Genzyme General (Nasdaq: GENZ) announced on November 27 that it has
entered into a license agreement for a class of small-molecule compounds
that may be useful in treating lysosomal storage disorders. The agreement
with the University of Michigan covers a series of U.S. and foreign
patents and patent applications related to certain ceramide-based compounds
and their therapeutic use. Terms of the agreement were not disclosed.
The novel compoundsprivation therapy, first conceived by Dr. Radin
over twenty years ago.
In pre-clinical testing, the most advanced of the compounds developed
by Dr. Shayman have demonstrated significant potency and specificity
advantages over first-generation compounds currently being investigated
for the treatment of lysosomal storage disorders. This means that they
may cause fewer of the side effects that have been observed with those
compounds. In addition, Dr. Shaymanmarket therapies for lysosomal storage
disorders utilizing a wide range of approaches to treating this family
of genetic diseases. Genzyme markets the enzyme replacement therapy
Cerezymegs also have the potential to address the central nervous system
effects of lysosomal storage disorders because they may be capable of
crossing the blood-brain barrier, which protein therapies cannot do.
Genzyme has its own internal small-molecule drug discovery program,
and also continually evaluates compounds under development elsewhere
for potential licensing opportunities.
Genzyme expects to complete pre-clinical development of the lead small-molecule
candidate within one year. A comprehensive pre-clinical plan is in place
to evaluate the toxicity and potency profile of this compound before
the initiation of human clinical trials. Genzyme has also established
a sponsored-research agreement with Dr. Shayman, under which he will
search for other small molecules that may be useful in treating lysosomal
storage disorders.
h for treatments for genetic disorders and has the expertise, resources,
and commitment to explore the promise of substrate-deprivation therapy.
We believe our approach could represent a significant advance over other
small-molecule candidates for substrate deprivation, which have more
limited activity and less specificity against glucosylceremide synthase.
Because of the lower specificity of these first-generation compounds,
they may cause frequent side effects that pose potential risks to patients.t
the action of glucosylceramide synthase, a key enzyme that initiates
the synthesis of a series of lipids. By reducing abnormal lipid accumulation
in involved cells, these compounds may address the pathology associated
with lysosomal storage disorders. Because the synthesis of an entire
pathway of lipids is inhibited, the compounds are expected to have application
in a range of lysosomal storage disorders.
The most advanced of these compounds has been shown in pre-clinical
studies to be significantly more potent and less toxic than other small
molecules in development for the treatment of lysosomal storage disorders.
This should allow the administration of smaller quantities of a drug
to achieve a therapeutic effect, and it may enable a broader range of
dosing.
Another potential key advantage of this molecule is its high specificity,
as it narrowly targets glucosylceramide synthase. First-generation substrate-deprivation
compounds are far less specific, acting on additional enzymes in lipid
and protein pathways. This lack of specificity may be associated with
some adverse events that have been observed in clinical studies of these
compounds.
Genzyme General develops and markets therapeutic products and diagnostic
products and services. Genzyme General has three therapeutic products
on the market and a strong pipeline of therapeutic products in development
focused on the treatment of genetic disorders and other chronic debilitating
diseases with well-defined patient populations. Genzyme General is a
division of the biotechnology company Genzyme Corporation.
Dr. Shayman is Professor of Internal Medicine and Pharmacology and
Associate Chair for Research Programs, Department of Internal Medicine,
University of Michigan. Dr. Radin is Professor Emeritus, Mental Health
Research Institute, University of Michigan.
This press release contains forward-looking statements, including statements
concerning the ability to use small-molecule compounds developed by
Dr. Shayman to treat lysosomal storage disorders, including related
central nervous system effects; the expectation that Dr. Shayman to
demonstrate that Dr. Shayman
