Rare Disease Day takes place on the last day of February each year to raise awareness about rare diseases and their impact on patients’ lives.

In the US, any disease affecting fewer than 200,000 people is considered rare. There are more than 7,000 rare diseases affecting 25-30 million Americans, according to the National Organization for Rare Disorders (NORD), the official sponsor of Rare Disease Day.

Besides dealing with the symptoms of the disease itself, rare disease patients frequently struggle to receive the right diagnosis and find options for treatment.

The rarity of their conditions also makes it more challenging to secure funding for medical research and to convince drug companies to invest in the development of new drugs that may only treat a small portion of the population.

Despite these challenges, researchers at Mass General are continuing to look for new insights into the causes of rare diseases and potential pathways to treatment. Here are a few examples of projects are investigators are working on:

Research Into Rare Scalp-Ear-Nipple Syndrome Leads to New Insights on Kidney Fibrosis

Alexander Marneros, MD, PhD
Cutaneous Biology Research Center
Associate Professor of Dermatology,
Harvard Medical School

Understanding the causes of even very rare diseases can result in important new findings that have implications for very common diseases.

A perfect example of this has been our research on an exceedingly rare syndrome, called Scalp-Ear-Nipple (SEN) syndrome.

This syndrome manifests with absence of nipples and breasts, as well as a scalp skin defect at birth. Notably, only about a dozen families with this syndrome have been described worldwide.

We aimed to identify the gene defect that causes this syndrome in order to learn more about the genes involved in the proper formation of skin, nipple and breast tissues.

Human genetics approaches identified a mutation in a novel gene (called KCTD1), whose function was previously completely unknown, in patients with SEN syndrome.

To study this gene further, we generated mice that lack KCTD1 and made the surprising discovery that these mice developed progressive kidney fibrosis and chronic kidney disease.

This suggests that KCTD1 is a major regulator of kidney function. Indeed, when reassessing patients with SEN syndrome we found that these patients also developed progressive renal failure as seen in the mice without KCTD1.

Our detailed studies in these mice uncovered a previously unknown critical role of the SEN syndrome gene KCTD1 for the ability of the kidney to concentrate urine and prevent renal fibrosis.

These findings have provided important new insights into how the kidney functions and prevents renal fibrosis.

Thus, our work on a very rare syndrome has led to novel clinically relevant findings that have broad implications for some of the most common clinical diseases, namely renal fibrosis and chronic kidney disease.

Our discoveries may result in better treatment options for patients with these common kidney diseases that affect millions of patients.

Searching for Genetic Clues to a Devastating Childhood Disease

Susan Cotman, PhD
Center for Genomic Medicine
Assistant Professor of Neurology, Harvard Medical School

Our research is focused on the group of rare diseases known as Neuronal Ceroid Lipofuscinosis (NCL), or Batten disease.

These are fatal, inherited disorders in which a genetic defect impairs a cell’s ability to recycle certain molecules.

Most forms of Batten disease/NCLs begin during childhood, and children with the disease often appear normal before the onset of symptoms such as vision loss, seizures, loss of skills, dementia and abnormal movements.

Eventually children with Batten disease become blind, wheelchair-bound, and lose all cognitive functions, including the ability to communicate.

Using a variety of genetic disease models, we have uncovered an important role for lysosomal calcium in the form of Batten disease caused by CLN3 mutations.

Together with my Mass General colleague, Yulia Grishchuk, PhD, we are studying the potential for altering the activity of lysosomal calcium channels to slow or prevent CLN3 disease progression.

Genomic medicine discoveries in recent years have demonstrated clear overlaps between Rare Disease and those that are more common.

As a result, Rare Disease research provides an opportunity to both advance therapeutic developments for Rare Disease patients and to impact scientific progress in more common disease areas with overlapping biology.

About the Mass General Research Institute
Research at Massachusetts General Hospital is interwoven through more than 30 different departments, centers and institutes. Our research includes fundamental, lab-based science; clinical trials to test new drugs, devices and diagnostic tools; and community and population-based research to improve health outcomes across populations and eliminate disparities in care.
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