Earlier this year, the Lysosomal Storage Disease Research Consortium awarded its first seven grants, which together total more than $200,000, to scientists conducting research into ameliorating the effects of lysosomal-storage diseases on the central nervous system. There are more than 40 of these diseases, called LSDs, including Tay-Sachs, Gaucher disease, mucopolysaccharidosis (MPS) and Niemann-Pick disease.
The consortium maintains a collaborative relationship with the National Institute of Neurological Disorders and Stroke, a branch of the National Institutes of Health. Scientists whose grants are rejected by NINDS have the option of applying for an LSDRC grant to obtain further data, with the understanding that, after more research, they will reapply for the original NINDS grant.
“The beauty of this is that our money helps to facilitate their research, such that they have results that would allow them to apply to the NIH and get the larger money,” said Barbara Wedehase, the executive director of the National MPS Society. It and the National Tay-Sachs & Allied Diseases Association initiated the consortium, though several other LSD organizations now participate as well.
Those who suffer from LSDs lack an enzyme — which enzyme is missing depends on the disease — necessary for cellular processes to occur properly. What results is the accumulation of unwanted material in the lysosome, a part of the cell. The results can range from joint pain and anemia (in the case of Gaucher) to limited motor function and even death (in the case of infantile Tay-Sachs).
The consortium arose with the realization that “by joining funds together, we would be able to serve a greater number of people,” Wedehase said. Dr. Mark Sands, who sits on the LSDRC’s grant-review committee, noted the consortium’s utility: “The underlying biology is really very similar” among the several LSDs, he explained. “Discoveries in one field could really impact dramatically other diseases.”
The majority of LSDs sufferers have neurological symptoms. “The brain remains the most difficult challenge,” said Dr. Mark Haskins, the chair of the Grant Revi
Focusing research on the brain would appear to favor Tay-Sachs, which is largely neurological, as opposed to Gaucher, whose sufferers exhibit no neurological symptoms. Both diseases disproportionately afflict Ashkenazic Jews. One grant recipient is Dr. Synthia H. Mellon, of the University of California, San Francisco. She is investigating whether neurosteroids, a class of compounds derived from cholesterol, can be used to replace the product that would otherwise be created by the missing enzyme in an LSD patient — in this case, a Tay-Sachs patient. NINDS turned her down; she’s currently using her LSDRC grant to obtain further data from animal models.
“This consortium was willing to take the chance, to see, Will it work or not?” Mellon said. “And if it does work, there will hopefully be a bigger payoff.”
Haskins said that the LSDRC was a step in the right direction, but not a panacea. “It’s not the one-bullet theory, where if you solve one LSD you solve them all,” he said. “But any insights we can gather on how to improve function in LSDs will spill over into other LSDs.”