Rare Disease Report sat down with Brian Wamhoff, PhD, Head of Innovation at HemoShear Therapeutics, to discuss what the company is doing throughout the rare disease community and why it could have such an incredible impact in the near future.
Brian Wamhoff, PhD
Brian Wamhoff, PhD, Head of Innovation serves as HemoShear Therapeutics' Head of Innovation and is a founder of the company. He is responsible for development and management of strategic team initiatives to ensure a robust pipeline of disease models to advance its drug discovery platform and early stage therapeutic programs. He has led teams to oversee the successful development of human vascular and liver disease models, as well as ongoing development of a tumor microenvironment system.
These advancements have been built in part by his role in securing significant National Institute of Health (NIH) Small Business Innovation Research funding from 5 different NIH institutes.
Rare Disease Report sat down with him to discuss in greater detail what the company is doing throughout the rare disease community and why it could have such an incredible impact in the near future.
RDR: Can you provide me with a brief overview of HemoShear Therapeutics?
Brian Wamhoff: HemoShear Therapeutics is a biotechnology company focused on discovering and developing drugs to treat children’s rare metabolic disorders. Our goal is to discover drugs that improve the lives of children who are born with metabolic defects and are unable to sustain basic biochemical processes necessary for life. Our proprietary technology allows us to recapitulate diseases using cells of children born with genetic defects, interrogate the disrupted biochemical processes, explore drug intervention strategies, and select drug candidates that we believe have high probabilities of clinical success.
RDR: What is HemoShear doing in the rare disease arena? How is the company’s work contributing to advancing the development of rare disease therapies?
Wamhoff: HemoShear has recreated the human disease biology of several rare diseases called inborn errors of metabolism; this enables our scientists to understand the complex disease process, identify and validate promising treatment approaches, and study the effects of drug candidates. It is important to note that for the diseases we study, no effective pharmaceutical treatment options are available. This is due in part to the lack of experimental models to study these diseases, a problem that we have solved through our innovative platform.
RDR: What rare diseases are HemoShear focused on?
Wamhoff: HemoShear’s transformational disease models are accelerating the discovery of new treatments for three rare inborn errors of metabolism -- Propionic Acidemia (PA), Methylmalonic Acidemia (MMA) and Maple Syrup Urine Disease (MSUD).
RDR: Can you explain rare metabolic diseases in greater detail?
Wamhoff: Rare metabolic diseases like PA, MMA and MSUD are genetic disorders caused by the deficiency of certain enzymes required to metabolize amino acids, leading to the rapid buildup of life-threatening toxins in the body. These debilitating diseases cause a range of symptoms, including lethargy, irritability and poor feeding, and result in developmental delays, brain damage and even premature death due to heart failure. While some symptoms of these diseases can be controlled by dietary restrictions, there are currently no effective treatments available that significantly improve their quality of life or lifespan.
RDR: Can you explain what HemoShear’s transformational disease models are and any significant benefit they offer over traditional methods, like an animal model or static cells?
Wamhoff: Rare metabolic diseases are uniquely human and are often not recreated effectively in animal models. Nor can these diseases be well understood by traditional cell culture methods. Because of these limitations, there have been no breakthroughs in the understanding of the metabolic disease process or ways to circumvent the inborn errors of metabolism until now. HemoShear’s REVEAL-Tx platform was designed to recreate the human disease condition. Our technology applies principles of physiological blood flow to tissue from the livers of metabolic disease patients who had their diseased organ replaced through transplantation. REVEAL-Tx restores the in vivo disease state to enable unprecedented insight into complex disease pathways. In combination with advanced computational tools, the platform accelerates the testing of treatment hypotheses and reduces risk of failure by identifying meaningful drug targets that can be assessed under more accurate disease conditions. Based on the insights generated by our platform, we are in the process of validating chemistries for multiple drug candidates for PA and MMA.
RDR: Recently, HemoShear participated in the Society for Inherited Metabolic Disorders Meeting (SIMD) and presented data on 3 diseases of rare inborn errors of metabolism: Propionic Acidemia, Methylmalonic Acidemia and MSUD. Can you discuss the data you presented?
Wamhoff: In 2015, we published the first ever propionic acidemia disease model using a patient’s liver cells. This model recapitulated many aspects of the disease. Since then, we have unmasked fundamental biology related to the disease that was previously unknown. At SIMD we presented some of this data, revealing to the scientific community a better understanding of how the energy cycle in cells of patients with propionic acidemia is impacted. Much of our understanding of this space was limited until now and these results help us understand clinical observations seen in these patients. Additionally, we unveiled our maple syrup urine disease model using liver cells from patients with the disease. We not only showed that we could detect measurable biomarkers of the disease but that current therapies being proposed for this disease will likely only work in a subpopulation of the patients. Our maple syrup urine disease model is currently being deployed for our own drug discovery portfolio to validate a potential drug target that could treat all MSUD patients.
RDR: What are the next steps for HemoShear in MSUD?
Wamhoff: HemoShear is currently validating a proprietary target for the treatment of MSUD. If successful, a drug discovery program will be launched.
RDR: Is HemoShear partnering with other organizations in the MSUD and metabolic disease communities? If so, who and what is their role?
Wamhoff: As we continue to make progress in researching rare metabolic diseases, HemoShear is open to dialogue with other companies who are active in this arena. For example, we could collaborate by combining our ability to model the disease process and interrogate treatment targets with companies developing new modalities, such as gene therapy.
RDR: Is there a message that you would like to deliver to the rare disease community on the advances being made in the rare disease field, particularly in rare metabolic diseases?
Wamhoff: Our message is that of passion and persistence. We are untangling very complex, rare diseases for which fundamental understanding is only now being unmasked for drug discovery. Our staff comes in every day dedicated to the mission of making meaningful discoveries that will propel us forward toward our goal of improving the quality of life for these patients. This should give us all hope for a better future for patients with metabolic diseases.