-- [ From: Bob Martone * EMC.Ver #2.5.3 ] --

Saw this today on the net. Looks like some more high potential PD
research is coming.


A Chance Finding Spurs Race To Develop Host of Nerve Drugs

Medical researchers have long dreamed of creating an elixir to
rejuvenate damaged nerves, restoring memory to Alzheimer's disease
victims and movement to the paralyzed. Now a chance finding may provide
the greatest hope to date in the quest to restore life to injured nerve
and brain cells.

A Chance Finding Spurs Race
To Develop Host of Nerve Drugs

April 21, 1998

Medical researchers have long dreamed of creating an elixir to
rejuvenate damaged nerves, restoring memory to Alzheimer's disease
victims
and movement to the paralyzed. But progress has come grudgingly.
Now a chance finding may provide the greatest hope to date in the
high-risk quest to restore life to injured nerve and brain cells.
Independent of one another, research teams at Johns Hopkins University
in
Baltimore and Oregon Health Sciences University in Portland recently
made
the surprising discovery that medicines originally developed to suppress
the immune system and fight organ-transplant rejection can also regrow
nerves in the spine or brain damaged by neurological diseases or
accidents.


Now several companies, including Guilford Pharmaceuticals Inc Vertex
Pharmaceuticals Inc. of  Cambridge, Mass., and  Pfizer Inc., are racing
to develop experimental nerve drugs, called neuroimmunophilins, that can
be used to combat the largely untreatable symptoms of illnesses such as
Parkinson's disease, Alzheimer's disease and stroke. Guilford, working
with Amgen  Inc., could begin human trials of a prototype drug based on
the research, to be tested in Parkinson's disease patients, within a
year. "This is compelling research," says Nicholas Saccomano, a director
of brain research at Pfizer's Groton, Conn., laboratory. "With leads for
Alzheimer's disease drugs few and far between, you'd have to be nuts not
to look into this." Drugs based on the serendipitous findings are still
years off, and their success is far from certain. After all,
neurological disorders are among the most mysterious and intractable
human maladies. Several years ago, two tiny biotechnology companies,
Cephalon Inc. and Regeneron Pharmaceuticals Inc., raised hopes among
patients and their families when  they spent tens of millions of dollars
testing genetically engineered nerve
drugs to treat patients with the lethal disorder called ALS, or Lou
Gehrig's disease. Cephalon is still seeking FDA approval for its nerve-
drug
Myotrophin.

Those trials ultimately ended in disappointment because the drugs
weren't very effective. Scientists are also troubled because the new
agents' nerve-reviving mechanism is still a mystery, a fact that many
drug
companies don't like to hear when investing in new science.

Creating a Stir

But the new research is generating excitement among paralyzed patients
and their families. Susan Howley of the American Paralysis Association
in
Springfield, N.J., says the neuroimmunophlins have caused a "stir" at
scientific meetings and appear to be a "legitimate area of inquiry."
The idea behind nerve-growth medications is simple and immensely
appealing. Most degenerative brain illnesses occur when important
neurons
die off over time or simply lose their ability to transmit electrical
signals to other cells. Researchers hope to develop drugs to protect
dying
nerves or revive those that are impaired.
Almost all previous attempts to restore nerves have used genetically
engineered versions of naturally occurring proteins the body uses to
spur
neuron activity. While these so-called growth factors work well in
laboratory tests, their impact in human trials has been minimal.

One big problem is that previous drugs like the ones from Regeneron and
Cephalon were large, unwieldy molecules that easily disintegrated in the
body and couldn't easily enter the brain or spinal cord. Thus for most
diseases they had to be injected directly into the brain or spinal cord
to
work, a difficult and risky procedure that has deterred many companies
from
even testing the drugs in humans.

The new nerve-growth agents, the neuroimmunophilins, have several
advantages over the older nerve drugs. They can be given orally,
suggesting
they will be able to slip easily from the bloodstream into the brain.
They
also appear to target only damaged nerves while leaving healthy ones
intact, suggesting they may have far fewer side-effects.
If they work, "it would be an extraordinary change in the way
neurological diseases are treated," says Fred Gage, a nerve regeneration
expert at the Salk Institute in La Jolla, Calif. "You'd have something
that
didn't just treat symptoms but actually altered the course of the
disease

Hunch Pays Off

The neuroimmunophilins were discovered four years ago by the laboratory
of Solomon Snyder, a noted brain scientist at Johns Hopkins, and other
scientists in Oregon. They were investigating the properties of FK-506,
then an experimental drug for organ transplantation (now sold as
Tacrolimus
by Fujisawa Pharmaceutical Co.). On a hunch, Dr. Snyder and his
colleagues
decided to examine FK-506's effects on brain cells. To their surprise,
they
found that brain cells contained 50 times more "receptors" for FK-506
than
did immune system cells, suggesting that FK-506 had a mysterious but
powerful biological role in the brain. Dr. Snyder's team was further
surprised when test-tube experiments showed that the transplant medicine
stimulated the growth of many types of damaged brain cells. "Not only
did it work, but it was unbelievably
potent," says Dr. SnyderMeanwhile, Bruce Gold, a young and then-unknown
neuroscientist at Oregon Health Sciences University, became curious
about the properties of FK-506 after his brother was treated with the
drug following a liver transplant. He noticed vague reports in the
medical literature that the drug interacted
chemically with molecules involved in nerve growth, and wondered if that
would affect nerve growth.

Not sure what would happen, he injected the compound into animals with
crushed leg nerves. The result "was absolutely surprising and unexpected
,"
he says. "The nerves responded to the drugs and the animals could walk
again sooner than they would have otherwise." Further laboratory animal
experiments revealed that FK-506, in fact, could help partially
regenerate
nerves in the spinal cord that are critical to motor control and don't
normally regrow.

Who Knows Why

Neither research team is certain why the new agents make cells grow. The
scientists guess they work in a way analogous to hormones, spurring
production of growth-boosting proteins and other chemicals normally
abundant only during the first years of life when expanding cell growth
is
needed.

FK-506's immune-suppressing action and numerous side-effects, including
increased cancer risk, kidney dysfunction and hypertension, made it
inappropriate for use in patients with chronic diseases. So researchers
at
Guilford Pharmaceuticals, which Dr. Snyder co-founded in 1993, located
the
portion of FK-506 responsible for the nerve-stimulating effects and
produced a series of drug-like molecules mimicking it. In tests on
animals
given a Parkinson's disease-like syndrome, the drugs appear to regrow
damaged nerves and cure the major symptoms of the disorder, Guilford
officials say.
The success of Drs. Gold and Snyder is spurring interest from larger
companies. Last year, Amgen called the neuroimmunophilins a breakthrough
in
brain biology and licensed Guilford's experimental drugs in a deal that
will give Guilford $48.5 million in cash and stock. Amgen's agreement
could
bring Guilford almost $400 million if the drugs eventually work.



--
Bob Martone(Nancy 53/23)