Cause, And Possible Treatments, For Hereditary Movement Disorder Discovered By E

[Guest guest]

(Note: Ataxia, and especially Frederich's Ataxia are often mimics of

CMT and some persons with CMT, have at one time been diagnosed with a

type of ataxia - myself included. ~ Gretchen)

Cause, And Possible Treatments, For Hereditary Movement Disorder

Discovered By Einstein Scientists

http://www.medicalnewstoday.com/medicalnews.php?newsid=38707

Researchers at the Albert Einstein College of Medicine of Yeshiva

University have discovered the underlying cause of a type of ataxia,

hereditary disorders characterized by poor balance, loss of posture

and difficulty performing rapid coordinated movement. Their work also

led to a drug that significantly improved the motor coordination in

mice with ataxia--a finding that could lead to better therapies for

the disease. The study appears in the March issue of Nature

Neuroscience and was featured in the publication's advance online

edition.

The research, led by Dr. Kamran Khodakhah, associate professor in the

department of neuroscience at Einstein, focused on a type of ataxia

called episodic ataxia type-2. It results from gene mutations that

affect calcium channels, which are involved in releasing

neurotransmitters in the brain and regulating excitability in

neurons. Episodic ataxia type-2 was thought to be due to impaired

transmission of neurotransmitters, but the Einstein scientists

suspected that something else was going on.

They studied specialized cells in the brain's cerebellum called

Purkinje cells, which are rich in calcium channels. Purkinje cells

help coordinate movement by acting as information clearinghouses:

They take in sensory and other inputs relayed to them by more than

150,000 excitatory and inhibitory synaptic inputs, combine them with

the cello's own intrinsic activity or " pacemaking, " and then send out

the signals necessary for motor coordination.

The researchers investigated whether ataxia might be due to a

reduction in the precision of the intrinsic pacemaking by Purkinje

cells. Studying a number of mouse models of ataxia type-2, they found

a gene-dependent loss of the precision of pacemaking in Purkinje

cells, which prevented them from accurately accounting for the

strength and timing of synaptic inputs when sending out signals

directing muscle movement.

This loss of pacemaking precision was traced to reduced activity of

calcium-activated potassium channels in Purkinje cells -- a direct

consequence of the reduced activity of calcium channels in these

disorders. Einstein researchers were able to remedy this problem with

a drug called 1-ethyl-2-benzimidazolinone (EBIO). When EBIO was

infused into the brains of ataxic mice, the mice's motor coordination

improved significantly.

" These calcium-activated potassium channels proved to be a potent

therapeutic target, since chronically activating them with EBIO

definitely improved the motor performance of these ataxic mice, " says

Dr. Khodakhah, who was senior author of the study. " We don't really

have effective treatments for these types of ataxia, so we're hopeful

that our findings will lead to drugs that will improve the lives of

people with this condition. "

Dr Khodakhah has established collaborations with two neurologists, Dr

Joanna Jen (UCLA) and Dr Strupp (Germany) to explore the

potential use of similar drugs in patients. The other Einstein

researchers involved in the study were Joy T. Walter, Karina Alvina,

D. Womack and Carolyn Chevez.