COI’s Focus on Rare Disease

There are more than 7,000 rare diseases affecting millions of people all over the globe.  These diseases, which tend to be genetic, are designated rare when a disorder affects fewer than 200,000 Americans.  Due to the limited number of people affected, awareness that can drive research and funding for development of therapeutics is often lacking.  As a result, most of these diseases have no approved treatments.

In an effort to increase awareness of these conditions, Rare Disease Day was established in 2008 and is now celebrated internationally on the last day of February.  At COI, we are joining in the efforts to spread awareness of rare diseases and the need for more research and development of therapeutics.

One of our requirements for pursuing a project is that it meets a critical unmet need in the medical community. As such, two of our companies, Calporta and Iron Horse Therapeutics, are developing therapeutics that could address two rare diseases, Niemann-Pick C Disease (NPC) and Amyotrophic Lateral Sclerosis (ALS), respectively.

Treating the Disease Not the Symptoms

NPC is a rare genetic disease that belongs to a larger family of conditions called lysosomal storage disorders.  These diseases arise when the body cannot properly transport or store fatty lipids such as cholesterol. With NPC, the fatty molecules accumulate in various tissues throughout the body leading to tissue damage and loss of function.  NPC is estimated to occur in one in 100,000-120,000 live births and the severity of the disorder ranges from immediately life-threatening to chronic and progressive throughout several decades depending on age of onset and diagnosis. Current treatment for this disease focuses on the symptoms that occur as a result of the tissue damage.

Calporta is taking a different treatment approach by targeting one of the underlying molecular components associated with NPC.  The company is working to develop a small molecule drug that can activate TRPML1, a key regulator in the transport of lipids and has been shown to be impaired in NPC. Increasing TRPML1 activity could help to normalize lipid trafficking and function.  While NPC is the primary disease focus for Calporta, modulation of TRPML1 may have implications in helping to treat other rare diseases such as muscular dystrophy.

Challenge Accepted

ALS, also known as Lou Gehrig’s disease, is a rare motor neuron disease that is characterized by progressive degeneration and death of nerve cells that control motor functions. This leads to eventual paralysis due to loss of motor control in all muscles of the body.  This disease affects about 30,000 people in the United States and, while there are several theories, the exact cause of ALS is yet to be determined. Current treatment for ALS is a multidisciplinary approach consisting of symptom control, physical therapy, and proper nutrition.  The only approved drug for ALS, riluzole, has been shown to extend survival by three to five months, but it does not have a substantial effect on muscle deterioration.  Clearly, there is still a need to develop therapeutics that help slow the progression of this disease.

Iron Horse Therapeutics is working to prolong survival and reduce disease severity by modulating the activity of the neuron-associated protein Epha4.  When Epha4 activity is increased in ALS animal models, loss of motor neurons is enhanced.  Conversely, inhibiting Epha4 activity indicates an increase in survival and reduction in the severity of the disease.  Based on this evidence, Iron Horse is developing compounds that could inhibit this activity and improve disease outcomes for ALS patients.

ALS has garnered special attention on social media that last few years during the #IceBucketChallenge, which occurs in August and is dedicated to raising money to fund research on this disease.  See how Iron Horse founders commemorated the company launch by accepting the challenge (watch the video!).

Room for Improvement

With all rare diseases there remains unanswered questions, lack of therapeutics, and daily anxiety for patients and their families.  At COI, we will continue to investigate therapeutics in hope of offering meaningful advances in these often overlooked diseases.

Visit to learn more about Rare Disease Day and how to get involved.