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Medications for neurodegenerative diseases

Medications for neurodegenerative diseases


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Medications for neurodegenerative diseases

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Content Reviewers:

Yifan Xiao, MD

Huntington disease, or HD, is a rare neurodegenerative disease that involves a repeated sequence of DNA that causes an abnormal protein to form, leading to abnormal movements and cognitive problems.

In most people, a gene called huntingtin or HTT on chromosome 4, contains a triplet repeat, where the nucleotides C, A, and G are repeated 10-35 times in a row. In people with Huntington disease, this repeat goes on for 36 or more times in a row.

CAG codes for the amino acid glutamine, so people with Huntington disease will have 36 or more glutamines in a row in the huntingtin protein.

So, in addition to being a triplet repeat disorder, HD is, more specifically, a “polyglutamine” disease.

The specific way in which extra glutamines causes HD symptoms isn’t fully worked out, but some clues are that the mutated protein aggregates within the neuronal cells of the caudate and putamen of the basal ganglia causing neuronal cell death.

Cell death might be related to excitotoxicity, which is excessive signaling of these neurons, which leads to high intracellular calcium.

Now the symptoms of HD involve progressive CNS disturbances including movement, cognitive, and mood symptoms and they start appearing around the age of 40.

Remember, the age of onset depends on the number of CAG repeats, so more repeats means earlier onset.

Over time, if enough of the neurons die in the caudate and putamen, which together form the dorsal striatum, then it can cause actual loss of brain tissue volume in that area and expansion of the lateral ventricles.

The death of neurons also cause neurotransmitter imbalance in these regions and there’s a decrease in inhibitory neurotransmitters like GABA, and an increase in stimulatory neurons like dopamine.

This also decreases acetylcholine, which is released by interneurons that help other neurons communicate.

Now, the affected areas play an important role in movement, particularly inhibiting it, so cell death in the basal ganglia causes movement problems like chorea, which are purposeless, dance-like jerking movements, and athetosis which are slower, writhing, “snake-like” movements mainly affecting the hands.

These involuntary movements can’t be consciously suppressed and stop only with sleep.

Other motor problems include abnormal eye movements and poor coordination.

Loss of tissue in these regions can also lead to psychological problems as well.

These people often experience psychosis and agitation, leading to disruptive behavior, and mood disorders like major depressive disorder.

They might also develop dementia and severe cognitive defects.

Since the muscles for swallowing become discoordinated, these people often suffer from dysphagia and aspiration pneumonia.

Unfortunately, there is no treatment to stop or reverse Huntington disease, and death usually happens within 10-20 years of diagnosis, often by aspiration pneumonia or suicide.

The medications used for Huntington disease are focused around managing the symptoms like chorea, and psychosis.

Since dopamine is increased in the regions of the brain affected, medications that lower dopamine levels or act as antagonists are usually used. These include tetrabenazine, and antipsychotics.

Let’s start with tetrabenazine and its deuterated form, deutetrabenazine.

Deuterated simply means some of the hydrogen molecules in the medication have been replaced by the more stable deuterium isotope to improve the half life of the drug.

These medications work on both presynaptic and postsynaptic neurons.

In the presynaptic neuron, they block vesicular monoamine transporters, or VMAT found on the vesicles.

These transport proteins allow dopamine into the vesicles for storage, so when they are inhibited, the vesicles can’t release dopamine into the synaptic cleft.

Next, on the postsynaptic neuron, these medications act as a weak dopamine receptor antagonist, so they bind to the receptors and prevent dopamine from binding.

Tetrabenazine and deutetrabenazine are often used for the treatment of chorea in Huntington disease. However, they are also useful for treating Tourette’s syndrome, which is a neurological disorder characterized by repetitive, involuntary movements and vocalizations called tics.


There are a few different types of medications that can be prescribed for neurodegenerative diseases. One common type is called cholinesterase inhibitors, which work by preventing the breakdown of the neurotransmitter acetylcholine. This type of medication can help to improve cognitive function and memory in people with Alzheimer's disease.

Another common type of medication for neurodegenerative diseases is NMDA receptor blockers. This type of medication helps to prevent damage to nerve cells by blocking the action of glutamate, a chemical that can be harmful to nerve cells. Blocking glutamate can help to preserve nerve function and reduce symptoms in people with conditions such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.

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