Rare Disease Report&reg Editorial Staff

#5: Hartmann Wellhoefer, MD, on Challenges Faced & Advances Made in Fight Against MPS

, Hartmann Wellhoefer, MD, vice president of medical affairs, Rare Diseases and Internal Medicine, at Shire, discussed the biggest challenges faced and advances being made in the fight against mucopolysaccharidosis (MPS), a group of rare, hereditary, and incurable conditions for which only a handful of treatments are available.

Dr. Wellhoefer also highlights key takeaways from the 15th International Symposium on MPS and Related Diseases (ISMPS) which was held from August 2-4, 2018 in San Diego, California. Through the symposium, the MPS community was provided with an opportunity to learn more about the latest research being conducted in the field as well as share personal experiences to boost awareness and improve patient care.

:  You recently attended the 2018 International Symposium on Mucopolysaccharidosis (MPS) and Related Diseases. Can you tell me about this conference?

Dr. Wellhoefer:  The ISMPS is one of the most unique congresses I’ve ever attended because of the presence of patient advocacy groups, patients, their families, and caregivers, as well as physicians and industry representatives. You actually hear children chatting and laughing in the hallways of the Congress, and more importantly, in the scientific sessions. It is these sounds that remind you it is all about the patient. This mix gives the event a very different atmosphere—almost a lightness, despite the fact that we’re talking about very serious and often life-threatening diseases.

At this Congress, there is also a tangible sense of hunger for new information. You walk the hallways and you see a global medical expert speaking with a patient and/or caregiver, having earnest conversations about MPS and sharing their perspectives.

The experience of attending and participating in this conference reinforces some of the major challenges of working in rare diseases, like MPS. Each of the MPS diseases—7 in total&mdash;are all very different in terms of the onset and type of symptoms. At ISMPS, because of the patient presence, you are able to see the individuality in each patient&mdash;or, to put it in medical terminology&mdash;the different phenotypes within each of the MPS diseases. This high level of variability within the same disease is the very challenge we have across almost all of the 7,000 or so rare diseases, some of which have treatments, most of which do not. This reminds us that there is much work to be done and that we have our work cut out for us&mdash;as an industry, and as a leader in rare diseases.

#4: Children with Acute Lymphoblastic Leukemia May Be Immunologically Disparate at Birth

, on challenges faced and advances made in the fight against MPS.

Investigators in Denmark have found new evidence suggesting that children who develop acute lymphoblastic leukemia may be predisposed from birth, and their immune responses to early childhood infections may offer clues to how the disease develops.

Childhood acute lymphloblastic leukemia (ALL) is a cancer of the blood and bone marrow originating in the T and B lymphoblasts in the bone marrow. In children with ALL, the bone marrow makes too many immature lymphocytes, and the immune system weakens. With a decrease in healthy red blood cells, white blood cells, and platelets, children can experience infections and anemia and may bleed easily. According to the National Cancer Institute, rates of childhood ALL have been on the rise along with other childhood cancers since 1975. It is the most commonly diagnosed cancer in children, making up about 25% of all cancer diagnoses in children under the age of 15 years.

With remission rates of about 98% and a 90% survival rate at 5 years, children with ALL today benefit from advances in treatment. Many symtpoms of ALL are similar to other conditions and can include aches in the arms and legs, unexplained bruising, enlarged lymph nodes, unexplained fever, tiredness, unexplained weight loss, and prolonged bleeding from minor injuries. Risk factors for children developing ALL include prenatal exposure to x-rays, post-natal exposure to high levels of radiation, chemotherapy treatment, inherited genetic variants, and genetic conditions including Down syndrome.

, a research team led by scientists at the Statens Serum Institut in Copenhagen, Denmark, explored the hypothesis that children with ALL are born with a dysregulated immune function that together with postnatal environmental exposures causes the development of the disease in childhood. Previous studies had indicated that children could develop ALL due to an overreaction to childhood infections.

#3: Positive Preliminary Phase 2 Data Reported for DLBCL Combination Therapy

children with acute lymphoblastic leukemia

 may be immunologically disparate at birth.  

IMV Inc. recently announced positive preliminary data collected from its phase 2 clinical trial evaluating a combination therapy consisting of anti-cancer immunotherapy, DPX-Survivac, in combination with low dose cyclophosphamide and Merck’s pembrolizumab (Keytruda) for the treatment of diffuse large B-cell lymphoma (DLBCL). The therapy was found to have an acceptable safety profile, with patients showing tumor regression and/or stable disease. 

“This type of lymphoma remains a significant unmet medical need in today’s treatment landscape,” Frederic Ors, BSc, MSc, chief executive officer of IMV Inc., told 

. “There is a poor prognosis for DLBCL patients who are not cured by first-line chemotherapy, and there is an increasing incidence of the disease in elderly patients who often cannot tolerate the current standard-of-care.”

Investigators anticipate enrolling 25 participants whose DLBCL expresses survivin—a tumor antigen expressed in more than half of patients with the cancer&mdash;in the phase 2, interventional, open-label, single group assignment trial. Data pertaining to the first 4 evaluable participants were included in the announcement.

“DLBCL has an overexpression of the survivin protein—in approximately 60% of patients, I believe,” Ors explained. “DPX-Survivac’s mechanism of action targets survivin and elicits a cytotoxic T cell immune response against cells presenting survivin peptides. Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in many cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to anti-cancer therapies.”

#2: Myeloproliferative Neoplasms Impair Patient Employment Status & Work Productivity

Read more about the positive preliminary phase 2 data reported for the potential 

While a pronounced symptom burden is not remarkable for patients with myeloproliferative neoplasms (MPNs), a recent study investigating the impact of MPNs on employment status, career potential, and work productivity is since few studies have investigated the rare blood cancers’ effects on patients’ professional lives.

, investigators found patients with MPNs experience changes in employment status and meaningful impairments on work productivity and activities of daily living, with the degree of impairment reflecting the severity of symptom burden.

For their research, the investigators recruited US respondents aged 18 to 70 years of age who have been diagnosed with MPNs, including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) to participate in their cross-sectional Living with MPNs survey. The survey included 100 questions related to MPN diagnosis, disease-related medical history, MPN-related symptoms and functional status, changes in employment and work productivity, and impact on daily activities since diagnosis.

Symptom burden was assessed by The MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), while the effects of MPNs on work productivity and activity (7-day recall) among currently employed respondents was assessed by The Work Productivity and Activity Impairment Specific Health Problem questionnaire (WPAI-SHP). Spearman’s coefficients were used to calculate correlations between MPN-SAF TSS and WPAI-SHP scores.

#1: Robert J. Kreitman, MD, on New Kind of Treatment for Hairy Cell Leukemia

 impair patient employment status and work productivity.

This month, the US Food and Drug Administration (FDA) approved the first new treatment option for hairy cell leukemia (HCL) in over 20 years—AstraZeneca’s moxetumomab pasudotox (Lumoxiti), a new kind of treatment developed to fulfill an unmet need for patients with the rare blood cancer whose disease has progressed after trying other approved therapies.

), Robert J. Kreitman, MD, lead investigator on the drug’s phase 3 clinical trial, provided insight on what makes the CD22-directed cytotoxin so unique as well as the clinical implications of its approval.

 Can you discuss Lumoxiti? What makes the treatment unique? 

Dr. Kreitman: It’s an idea that goes back several decades—taking an antibody or part of an antibody and partnering it with a toxin so that the antibody will bind to a target on the cancer cell, go inside, and then the toxin [will] kill the cell. In Lumoxiti, the toxin comes from 

 bacteria—it’s a very powerful toxin.

Can you discuss the phase 3 trial of Lumoxiti?

We had a preliminary meeting with the FDA back in 2012 where we planned out what we needed to achieve in order to have the drug approved. We knew back then that it had good activity, but we received good feedback from the FDA about what kind of trial would be acceptable to design.

We designed a trial where everyone who entered into the trial would receive Lumoxiti at a fixed dosing level. We decided we would observe the treated patients for toxicity and efficacy, and if they achieved a certain complete remission rate that was durable enough. In other words, we observed whether the patient had improved blood counts for at least 6 months—that counted towards what we called the primary endpoint.

We met the primary endpoint, and the FDA, therefore, approved the drug.

, on new HCL treatment, moxetumomab pasudotox (Lumoxiti).

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Top 5 Rare Disease News of the Week&mdash;September 23, 2018

Dr. Wellhoefer also highlights key takeaways from the 15th International Symposium on MPS and Related Diseases (

) which was held from August 2-4, 2018 in San Diego, California. Through the symposium, the MPS community was provided with an opportunity to learn more about the latest research being conducted in the field as well as share personal experiences to boost awareness and improve patient care.

The ISMPS is one of the most unique congresses I’ve ever attended because of the presence of patient advocacy groups, patients, their families, and caregivers, as well as physicians and industry representatives. You actually hear children chatting and laughing in the hallways of the Congress, and more importantly, in the scientific sessions. It is these sounds that remind you it is all about the patient. This mix gives the event a very different atmosphere—almost a lightness, despite the fact that we’re talking about very serious and often life-threatening diseases.

What were some of the major topics of discussion at the conference, and your biggest takeaways?

Front and center was the importance of patient engagement and the role of patients and caregivers as the champions of their own diseases. As a biotechnology company focused on rare diseases, it is absolutely critical to give patients the option to be included in what we are doing. More specifically, it is essential to include the voice of the patient in the drug development process. 

 (PRO) really help in this regard to quantifying what’s important for an individual patient as far as his or her symptoms, reactions to the drug and the way he or she experiences the efficacy of a drug in a clinical trial setting. We want to—and have to&mdash;capture that in a quantitative way to help guide us in the drug development process.

The same applies to caregiver engagement. MPS diseases largely affect children, so how the caregiver sees the disease—and what problems or symptoms are important to them&mdash;might differ from what’s important to physicians and researchers.

To give you an example relating to Hunter syndrome (MPS II), from some parents’ perspective, the behavioral aspects of the disease are much more important than the neurocognitive aspects, including IQ. Caregivers see behavioral changes over time—such as aggression, or just the way MPS II boys connect with their environment&mdash;and for the parent, while a potential IQ decline is devastating, the child’s behavior can be a much bigger concern day-to-day.

We heard a lot about this theme during the conference.

What are some of the recent advances in MPS that have made a difference in the lives of physicians, patients, and their family members/caregivers?

There is a lot of talk about gene therapy. At Shire, we are also active in this field—looking at gene therapy as a potential option for the treatment of rare diseases. Overall, the discussions and presentations about it were cautiously optimistic about potential progress, but there remains quite a bit of healthy skepticism. The hurdles in gene therapy are still quite daunting.

What are the biggest challenges and hurdles for the MPS community and how are these being addressed?

There is a true hunger for updates, especially in terms of advances in treatment. In particular, patients and their families want to know how potential new therapies, delivery systems, or approaches can address the central nervous system (CNS) part of MPS diseases, such as cognitive decline, behavioral changes, impaired mobility, etc.

As many people know, about 9 months ago we shared some disappointing top-line results from our investigational intrathecal program (SHP609) for MPS II. SHP609 has not been approved for use by the US Food and Drug Administration, European Medicines Agency, or any other regulatory authorities. Our research and development team is working in close collaboration with the investigators, experts in the field, and regulatory authorities such as the FDA on a potential path forward. And we are continuing the extension study for this program.

Why is designing clinical trials for a rare disease such as MPS a major challenge? How are these challenges being addressed?

Clinical trials, in general, can be a challenge, but when you have just a small number of patients affected by a rare disease, the challenges multiply.

The first challenge is finding a homogenous group of patients—patients who have a similar set of symptoms, a similar history, and severity of the disease. Even if a group of these patients exists, they may not be located near a health care facility that includes physicians who have experience running clinical trials in rare diseases and administering investigational therapies.

The second challenge is demonstrating that the drug is effective and safe by determining endpoints that are meaningful for the patient, the family, the caregivers, and for regulatory authorities, as well as the institutions that will hopefully reimburse the drug at some point in time. In rare diseases, these endpoints are typically not well understood.

The third challenge in diseases like MPS is the fact that there may be a small window of opportunity to make a difference for patients who are rapidly deteriorating. Part of our research is identifying if there is a “window in time” where decline could be slowed. For example, in MPS II this might mean a young boy starts showing physical and behavioral symptoms but otherwise appears to be in a rather healthy cognitive status. In this scenario, there may be an opportunity to help.

The other challenge is that these clinical trials are typically double-blind, placebo-controlled trials. But in the case of a rare disease, where there may be no available treatment options, is it ethically and morally justifiable to provide some children with treatment and others with placebo with no opportunity to receive the investigational drug?

The good news is that regulatory authorities are more amenable to accept historical data and data from natural history studies to establish the natural course of a disease. However, we need to generate these natural history studies and establish what the course of the disease looks like to set as a comparator. It can be a race against the clock.

Can you elaborate on the importance of conducting more clinical trials in the rare disease space?

Clinical trials are the best approach to provide patients with a drug that we hope has the potential to be approved as safe and effective by regulatory authorities. Controlled clinical trials allow us to do everything we can to limit the potential risk to patients while finding signals for efficacy.

But what does efficacy mean? You may have to compare potential new drugs to standards of care—or, as is typical in rare diseases, to no treatment at all. And you may not be able to demonstrate efficacy in individual patients because each patient is different in terms of symptoms and stage of the disease. What might look like a signal of efficacy in one patient may end up being a reflection that he or she is relatively stable when compared with other patients, and not an indication of drug efficacy. And so, in order to establish efficacy, you need a very controlled environment&mdash;a clinical trial with a number of patients that may help assure researchers that what they observe is efficacy and not the natural history of individual patients.

Another essential part of this efficacy equation that is often forgotten is the dose. The clinical trials help us to establish if there is a safe and effective dosing level.

Unfortunately, we know that a lot of drugs that enter clinical trials are not successful. For example, on average only

 1 in 10 succeed in making it from phase 1 to approval

. These failures along the approval process can be for a number of reasons. Was the selected dose the right dose? Did the patient actually take the drug? If the drug is administered orally, you don’t always know. Was the right mechanism of action targeted? These are just some of the reasons that a drug may not make it to approval, which is why we need a controlled environment to identify these different variables.

Establishing safety, efficacy, and the right dose in a relatively small, homogeneous population is essential for gaining regulatory approval so that the treatment may be available to the larger patient population. While this may be a lengthy process from an individual patient or caregiver perspective, this process provides the fastest opportunity to find a viable treatment for as many patients as possible.

What is Shire’s mission in the rare disease space?

The rare disease community is relatively small compared to diabetes, hypertension, heart disease or oncology, but the unmet need is huge—their voices are strong, their mission is fervent, and their ability to work together to ensure advances in diagnosis, treatment, education, and support is incredible.

As a leader in rare disease, Shire wants to be the driving force in moving scientific innovation forward and finding and developing treatment options for unmet needs. We are committed to transparency and open engagement whenever possible and work every day to be a champion for patients, their families, and the community at large.

In a recent interview with Rare Disease Report®, Hartmann Wellhoefer, MD, discussed the biggest challenges faced and advances being made in the fight against MPS.
 

Hartmann Wellhoefer, MD On Challenges Faced & Advances Made in Fight Against MPS

#5: PROOF Registry Study Reaffirms Benefit of Using Pirfenidone to Treat IPF

There are only 2 antifibrotics currently available to treat patients with idiopathic pulmonary fibrosis (IPF), a progressive, deadly lung disease that is associated with a median survival time from diagnosis of 2 to 5 years: pirfenidone (Esbriet) and nintedanib.

Although clinical trials provide important safety and efficacy data associated with these treatments, restrictive inclusion and exclusion criteria can make it difficult to apply results to real-world populations of patients with the disease.

In an effort to provide data on longitudinal treatment outcomes in real-world populations, a team of investigators launched the PROOF registry, an observational study that has been ongoing since 2013 which has been dedicated to monitoring disease progression in patients with IPF.

#4: Study Discovers Link Between Butterfly Syndrome and Skin Cancer

An international team of investigators has made a discovery about the cause of autosomal recessive dystrophic epidermolysis bullosa (RDEB) that sheds light on how the disease leads to cancer in some patients and offers clues to potential new approaches to treatment.

Also known as butterfly syndrome, RDEB is a rare genetic condition affecting the skin, causing it to blister and easily form erosions from minor injuries such as scratching or rubbing. According to the National Institutes of Health (NIH), the overall estimated incidence of dystrophic epidermolysis bullosa in the United States is 6.5 per million newborns, with more severe autosomal recessive forms of the disease occurring in 1 per million newborns. In cases of the most severe form of the condition, Hallopeau-Siemens type RDEB (RDEB-HS), infants are often born with widespread skin blistering and erosion occurring during birth. Healing skin develops severe scarring, and, along with other complications, patients with the disease are at high risk for developing an aggressive form of squamous cell carcinoma (SCC) as young adults.

#3: Fingolimod Linked with Lower Relapse Rate in Pediatric Patients with Multiple Sclerosis

The only approved treatment for pediatric patients with multiple sclerosis aged 10 years through to adulthood, fingolimod (Gilenya) was linked with a lower rate of relapse and less accumulation of lesions on magnetic resonance imaging (MRI) over a 2-year period compared with interferon beta-1a in the phase 3 PARADIGMS trial.

However, a higher rate of serious adverse events was also associated with the treatment, underscoring the need for longer studies to assess the treatment’s safety and durability in pediatric patients with multiple sclerosis.

Results from the trial have recently been published in the 

Tanuja Chitnis, MD, principal investigator of the study, stressed the challenges of treating this patient population to 

 “These children and adolescents will have a higher relapse rate than the typical adult patients,” she said. “We and several other groups have shown there is a higher relapse rate in association with younger age. That is part of the challenge, and it shows the importance of having effective treatments in children.”  

#2: Rare Pediatric Disease Designation Granted to Stargardt Disease Treatment, LBS-008

fingolimod in pediatric patients with multiple sclerosis

The US Food and Drug Administration (FDA) has granted a rare pediatric disease designation to Lin BioScience’s LBS-008 for the treatment of Stargardt disease, an untreatable, inherited condition that can result in permanent vision loss in children.

"We continue to be encouraged by the regulatory support for LBS-008 and the opportunities provided by the Rare Pediatric Disease designation and the Priority Review Voucher Program," stated Tom Lin, PhD, MBA, MMed, CEO of Lin Bioscience, in a recent statement.

LBS-008 is a first-in-class oral therapy that has been developed to inhibit the buildup of toxins in the eye that cause Stargardt Disease and atrophic age-related macular degeneration (dry AMD), which is a condition that damages the retina.

#1: New Urine Diagnostic Test Offers Inexpensive Way to Detect Onchocerciasis

Onchocerciasis, also known as river blindness, may now be detectable through a urine diagnostic developed by investigators from the Scripps Research Institute. The test, a lateral flow immunoassay (LFIA) diagnostic, can detect the parasitic worms that cause the rare disease, possibly providing a diagnosis in real time.

"River blindness affects individuals both in Africa and Latin America, and because many of these endemic regions are difficult to access, what is needed in the field is an inexpensive point-of-care means to monitor the disease," Kim Janda, PhD, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at Scripps Research, said in a recent statement.

Monitoring and evaluation are key when it comes to current elimination efforts for onchocerciasis—interruption of disease transmission indicates that efforts are working.

Currently, a “skin snip” biopsy is the current gold standard for detecting the parasitic worms; however, they are usually insensitive indicators of infection; as the density of microfilaria in the skin decreases, the sensitivity of the skin snip decreases. Other available tests are unable to distinguish between past and current infections.

The assay uses designer antibodies that are able to detect a unique biomarker—N-acetyl-tyramine-O-glucuronide (NATOG)&mdash;which only appears when a human host has metabolized tyramine&mdash;a worm neurotransmitter. Humans secret this biomarker in their urine. If a test comes back without any lines, the individual has the parasite; a negative test will show a colored line.

The discovery of NATOG as a biomarker for onchocerciasis was previously reported in human urine samples. NATOG bypasses the limitations of antibody biomarkers and PCR methodologies with its ability to distinguish between active and past infections.  

In the recent study conducted by the research team, the NATOG-based urine LFIA for onchocerciasis accurately identified 85% of analyzed patient samples (N = 27).

new urine diagnostic test for onchocerciasis

Top 5 Rare Disease News of the Week&mdash;September 16, 2018

#5 Accelerated Approval Denied & Pivotal Study Underway for Pompe Disease Treatment, AT-GAA

The US Food and Drug Administration (FDA) has denied Amicus Therapeutics’ accelerated approval for AT-GAA, a pipeline treatment for Pompe disease. However, per the FDA’s recommendation, plans for a pivotal study that is set to conclude this year are still underway, so approval could be forthcoming.

The decision followed a Type C meeting between the FDA and Amicus that discussed the regulatory path for AT-GAA. The upcoming, single pivotal study will compare AT-GAA to the current standard of care (alglucosidase alfa, an enzyme replacement therapy) and will serve as the study to support full approval.

Approximately 100 participants with Pompe disease are anticipated to enroll in the trial, which will include a population of both ERT-switch patients and ERT treatment-naïve patients. A 6-minute walk with a primary treatment period of up to 12 months will serve as the primary endpoint.

#4 Rhabdomyosarcoma Cellular Origins and Therapeutic Vulnerabilities Uncovered

Read more about the denied accelerate approval and pivotal study underway for Pompe disease treatment, 

Investigators from St. Jude Children’s Research Hospital have recently made strides in the fight against rhabdomyosarcoma, a rare childhood sarcoma that occurs in approximately 350 children and adolescents nationwide annually.

In the most comprehensive analysis of a common pediatric solid tumor to date, the team has identified weaknesses to target in the rare cancer, leading to a promising precision medicine treatment that has already hit clinical trials.

“Rhabdomyosarcoma patients with recurrent or metastatic disease represent a real clinical challenge with few patients achieving long-term survival,” Elizabeth Stewart, MD, co-first author of the study, said to 

. “Since there are not a lot of known druggable mutations in rhabdomyosarcoma, we aimed to identify tumor vulnerabilities that extend beyond somatic mutations in the genome.”

As additional therapeutic vulnerabilities are increasingly identified due to tumor-specific epigenetic perturbations that lead to altercations in gene expression, personalized cancer therapies aimed at targeting somatic mutations in patient tumors are increasingly entering into treatment approaches.

Since genomic and epigenomic changes ultimately manifest in the tumor proteome and phosphoproteome, Dr. Stewart and her team utilized transcriptomic, epigenomic, and proteomic/phosphoproteomic data to shed light on rhabdomyosarcoma’s cellular origins and therapeutic vulnerabilities.  

#3 Telavancin: Promising Treatment Option for MRSA in Cystic Fibrosis Patients?

Read more about the uncovered cellular origins and therapeutic vulnerabilities in 

 continues to plague patients in the health care and community setting, as well as the providers who treat them. When acquired in patients with cystic fibrosis, clinical outcomes are known to be even worse, resulting in an increased rate of declined respiratory function as well as infections that can have severe, and sometimes deadly, consequences.

For the first time, however, investigators have found that telavancin—a drug currently used to treat skin infections and hospital-acquired pneumonia&mdash;has potent 

activity and low resistance development potential when used against 

isolates in patients with cystic fibrosis, making it a promising potential treatment option for these patients.

“Telavancin (TLV) is a lipoglycopeptide antibiotic approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of complicated skin and skin structure infections and in 2013 for the treatment of cases of nosocomial pneumonia. However, its application for the treatment of CF-MRSA pneumonia infections was not known, so our studies are contributing to extend the application of TLV for CF treatment,” Adriana E. Rosato, PhD, associate professor in the department of Pathology and Genomic Medicine at Houston Methodist Research Institute told our sister publication 

#2 Fast Track Designation Granted to Idiopathic Pulmonary Fibrosis Treatment, Pamrevlumab

may be a promising treatment option for MRSA in cystic fibrosis patients.  

The US Food and Drug Administration (FDA) has granted a fast track designation to FibroGen, Inc’s pamrevlumab for the treatment of patients with idiopathic pulmonary fibrosis (IPF).

“This Fast Track designation reflects recognition of the great need for a new therapeutic to help patients diagnosed with IPF to reduce the burden and progression of this debilitating disease and another positive step in developing pamrevlumab for the treatment of IPF,” Elias Kouchakji, MD, senior vice president of Clinical Development and Drug Safety at FibroGen, said in a 

. “We look forward to advancing pamrevlumab into phase 3 studies early next year.”

Data from a randomized, double-blind, placebo-controlled 

 served as the basis for the designation. The main objective of the trial was to see if the treatment improved lung function; to do this, investigators measured the change in forced vital capacity (FVC) at weeks 12, 24, 36, and 48 and compared that data with the beginning of the trial.

Secondary objectives for the trial were to assess the progression of lung fibrosis, which they measured by using quantitative high-resolution computed tomography at weeks 24 and 48. The treatment’s safety and impact on quality of life were also evaluated.

#1 New Look at Gene Expression in the Brain May Offer Clue to Treating Huntington's Disease

Read more about the FDA;s fast track designation to IPF treatment, 

New research conducted by scientists from Lund University in Sweden is shedding new light on Huntington’s disease and the potential for new therapies for this and other neurodegenerative diseases.

 (HD), typically has an onset in adulthood and is marked by uncontrolled movements, emotional problems, and cognitive loss. The condition is caused by mutations in the 

, which provides instructions for the production of a protein called huntingtin that plays an important role in the brain’s nerve cells. This mutation leads to a buildup of protein aggregates in the nerve cells of the brain, thereby impairing their normal functions.

Autophagy is the biological process by which nerve cells break down and remove protein aggregates, a process which is disrupted in individuals with neurodegenerative diseases (NDDs), such as HD, Parkinson’s, and Alzheimer’s. In a recent 

, investigators set out to find if activating the process of autophagy can reverse the accumulation of the protein Argonaute-2 (AGO2) in neurons.

“We know very little about why protein aggregates arise or in what way they are involved in the development of the disease,” said the study’s lead author and head of the university’s Molecular Neurogenetics Jakobsson Lab, Johan Jakobsson, PhD, in a recent 

. “However, our study shows that expression of the mutated huntingtin gene impairs the nerve cells’ ability to break down and recycle cellular material, which results in an accumulation of the protein AGO2.”

By studying cell culture, mouse models, and human tissue from deceased HD patients, the investigators observed that AGO2 accumulation results in an increase in levels of microRNA (miRNA) levels, and that changes in the autophagy mechanism also resulted in extensive changes in microRNA activity. Their findings, according to the authors, indicate that impaired autophagy in Huntington’s disease and other diseases not only effects protein aggregation but also “directly contributes to global alterations of intracellular post-transcriptional networks.”

Read more about how a new look at gene expression in the brain may offer clues to treating 

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Rare Disease Report&reg Editorial Staff

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