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neurodegenerative disease

Huntington vs Parkinson’s Disease

Huntington vs Parkinson’s Disease

Is an abnormal protein the cause of Parkinson’s and Huntington’s diseases?

A group of researchers is looking into that question.

If successful, their research could lead to diagnostic tools and new treatments that could be used on both of these deadly neurological ailments.

“A possible therapy would involve boosting a brain cell’s ability to degrade a clump of proteins and damage vesicles,” explained Edward Campbell, PhD, study senior author, and an associate professor at Loyola, in a statement. “If we could do this in one disease, it’s a good bet the therapy would be effective in the other two diseases.”

 

What the scientists discovered

Neurodegenerative diseases are basically caused by the death of cells in the brain.

In Parkinson’s and Huntington’s, it primarily affects movement.

Despite those effectual differences, the Loyola researchers say they may have discovered a common thread among the trio of diseases.

In all three ailments, previous research has suggested that proteins that are abnormally folded form clumps inside brain cells.

Different proteins have been implicated in each of the three diseases. In Alzheimer’s, it’s tau. In Parkinson’s, it’s alpha-synuclein. In Huntington’s, it’s huntingtin.

The Loyola researchers concluded that these different proteins behave in the same way when they enter brain cells.

They said these proteins invade vesicles, small compartments that are encased in membranes.

The proteins damage those membranes, allowing them to then invade a cell’s cytoplasm and cause even more destruction.

The researchers said the damaged cells try to gather the ruptured vesicles and protein clumps together to destroy them. However, the proteins are resistant to the degradation.

“The cell’s attempt to degrade the proteins is somewhat like a stomach trying to digest a clump of nails,” Campbell said.

 

Huntington’s Disease

Huntington’s disease is a progressive brain disorder caused by a single defective gene on chromosome 4 — one of the 23 human chromosomes that carry a person’s entire genetic code.

This defect is “dominant,” meaning that anyone who inherits it from a parent with Huntington’s will eventually develop the disease. The disorder is named for George Huntington, M.D., the physician who first described it in the late 1800s.

The defective gene codes the blueprint for a protein called huntingtin. This protein’s normal function isn’t yet known, but it’s called “huntingtin” because scientists identified its defective form as the cause of Huntington’s disease. Defective huntingtin protein leads to brain changes that cause abnormal involuntary movements, a severe decline in thinking and reasoning skills, and irritability, depression and other mood changes.

 

Symptoms

Symptoms of Huntington’s disease usually develop between ages 30 and 50, but they can appear as early as age 2 or as late as 80. The hallmark symptom of Huntington’s disease is uncontrolled movement of the arms, legs, head, face and upper body. Huntington’s disease also causes a decline in thinking and reasoning skills, including memory, concentration, judgment, and ability to plan and organize.

Huntington’s disease brain changes lead to alterations in mood, especially depression, anxiety, and uncharacteristic anger and irritability. Another common symptom is obsessive-compulsive behavior, leading a person to repeat the same question or activity over and over.

 

Diagnosis

Scientists identified the defective gene that causes Huntington’s disease in 1993. A diagnostic genetic test is now available. The test can confirm that the defective gene for huntingtin protein is the cause of symptoms in people with suspected Huntington’s disease and can detect the defective gene in people who don’t yet have symptoms but are at risk because a parent has Huntington’s.

Experts strongly recommend professional genetic counseling both before and after genetic testing for Huntington’s disease.

 

Causes and risks

The defective gene identified in 1993 causes virtually all Huntington’s disease.

The huntingtin gene defect involves extra repeats of one specific chemical code in one small section of chromosome 4. The normal huntingtin gene includes 17 to 20 repetitions of this code among its total of more than 3,100 codes. The defect that causes Huntington’s disease includes 40 or more repeats. Genetic tests for Huntington’s disease measure the number of repeats present in an individual’s huntingtin protein gene.

Scientists don’t yet understand the normal function of huntingtin protein or how a few dozen extra repeats in its genetic blueprint lead to the devastating symptoms of Huntington’s disease. Researchers are eager to solve these mysteries to find the answer to Huntington’s. These solutions also may offer important insights into a wide range of other brain disorders, including Alzheimer’s, Parkinson’s disease and amyotrophic lateral sclerosis (ALS).

 

Treatment and outcomes

There is currently no cure for Huntington’s disease and no way to slow or stop the brain changes it causes. Treatments focus on managing symptoms. A group of international experts recommended the following treatments as first-line strategies for three of the disease’s most troubling symptoms:

  • Chorea (involuntary movements): Some experts believe beginning treatment with an atypical antipsychotic drug, such as olanzapine, is best. Others start with another type of drug recently approved by the U.S. Food and Drug Administration (FDA) specifically for Huntington’s, called tetrabenazine.
  • Irritability: For severe anger and threatening behavior, experts agree that an atypical antipsychotic drug is the preferred approach. For less severe, nonthreatening irritability, experts recommend first trying a selective serotonin reuptake inhibitor (SSRI), which is a type of antidepressant.
  • Obsessive-compulsive thoughts and actions: Experts also recommend SSRIs as the standard treatment for these symptoms.

Other Huntington’s symptoms, such as anxiety, depression and insomnia, also should be treated according to generally accepted guidelines. Experts encourage people with Huntington’s to keep all their medical appointments and not to get discouraged if it takes their health care team some time to find the best drugs and the most effective doses.

 

Physiotherapy Management

Physiotherapists working with these patients should take note of a recent finding

  • People with HD require extra time to carry out everyday tasks.
  • People with HD are forgetful but do not have a classical amnesia. They have the potential to benefit from memory aids.
  • Tasks, such as walking and talking, which under normal circumstances might be regarded as relatively “automatic”, require more conscious attention in people with HD. They are more demanding of attentional resources. It is important for people with HD to focus on one activity at a time.
  • People with HD may not initiate activities but with encouragement can engage successfully in them and experience enjoyment.

Standard physiotherapy for HD includes:

  • Gait re-education
  • Balance retraining
  • Fall prevention/management
  • Aerobic capacity
  • Muscle strengthening
  • Wheelchair prescription and training
  • Respiratory function
  • Task-specific reach, grasp, and manipulation

 


Parkinson’s Disease

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Parkinson’s disease (PD) is a neurodegenerative disorder that mostly presents in later life with generalized slowing of movements (bradykinesia) and at least one other symptom of resting tremor or rigidity. Other associated features are a loss of smell, sleep dysfunction, mood disorders, excess salivation, constipation, and excessive periodic limb movements in sleep (REM behavior disorder). PD is a disorder of the basal ganglia, which is composed of many other nuclei. The striatum receives excitatory and inhibitory input from several parts of the cortex. The key pathology is the loss of dopaminergic neurons that lead to the symptoms. It is the seconds most common neuro-degenerative condition in the world after Alzheimer’s.

Parkinson’s was described 3000 years ago in Indian and Chinese medicines with mainly plant-based remedies, however, James Parkinson was the first to describe it in the western medicine in his 1817 essay as the Shaking Palsy.

 

Etiology

PD Basal Ganglia etc.png

The condition is caused by the slow deterioration of the nerve cells in the brain, which create dopamine. Dopamine is a natural substance found in the brain that plays a major role in our brains and bodies by messaging and therefore communicating across various systems.

The cause of PD has been linked to the

  • Use of pesticides, herbicides, and proximity to industrial plants.
  • After injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (An accidental finding). This chemical accumulates in the mitochondria.
  • Oxidation and generation of free radicals causing damage to the thalamic nuclei.
  • Genes, the risk of PD in siblings is increased if one member of the family has the disorder. These cases also tend to occur much earlier in life.
  • The altered function of alpha-synuclein may play a role in the etiology of PD. Current research is focused on preventing the propagation and aggregation of alpha-synuclein

Epidemiology

  • Parkinson’s most often occurs after the age of 50 and is one of the most common nervous system disorders of the aging population.
  • PD affects 1 to 2 people per 1000 at any time. An estimated seven to 10 million people worldwide are living with Parkinson’s.
  • The prevalence increases with age to affect 1% of the population above 60 years.
  • 5% to 10% of patients have a genetic predisposition.
  • The incidence and prevalence of PD do increase with advancing age
  • The condition is more common in men than women.
  • In the UK, the prevalence of Parkinson’s is 145,519 with an incidence of 18,461 in 2018.

Interprofessional Management

PD is one of the most common motor disorders worldwide. The disorder has no cure and is progressive. The condition can present with motor abnormalities and a variety of psychiatric and autonomic problems. Almost every organ is affected by this disorder, and as the disease progresses, management can be difficult. An interprofessional team approach is the best way to manage the disorder.

Some non-motor aspects (sleep problems, low mood, constipation, and loss of sense of smell) occur several years prior to observable motor symptoms develop. Physiotherapists are most often involved in the mid-stages of the condition, once balance and mobility become affected, but it can be helpful if they can assess and advise people soon after diagnosis in order to maintain activity and prevent problems.

Besides physicians, nurses, pharmacists, social workers, and physical therapists play a vital role in the daily management of these patients. Parkinson’s creates complexities for health and social staff helping individuals and those affected by it (carers, family members, friends). Managing these complex issues is a challenge due to the varied combinations of a motor (movement) and non-motor symptoms presented throughout the course of the condition.

 

Common Motor Symptoms that Require Management

  • Tremor is a prominent and early symptom of PD (not always present and is not a necessary feature for diagnosis).
  • Slowness, or bradykinesia, a core feature of PD.
  • Rigidity is the third prominent feature on examination.
  • A combination of bradykinesia and rigidity leads to some other characteristic features of PD, such as micrographia.
  • The fourth prominent feature of PD is gait disturbance, although this is typically a late manifestation. Flexed posture, ataxia, reduced arm swing, festination, march-a-petits-pas, camptocormia, retropulsion, and turning en bloc are popular terms to describe the gait in PD. Gait disorder is not an early feature of PD but is frequently described as it is easy to recognize and cinches the diagnosis in later stages.

Complications to Address

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  • Depression
  • Dementia
  • Laryngeal dysfunction
  • Autonomic dysfunction
  • Kyphosis leading to cardiopulmonary impairment

Prognosis

The rate of progression of the disease may be predicted based on the following:

  • Males who have postural instability of difficulty with gait.
  • Patients with older age at onset, dementia, and failure to respond to traditional dopaminergic medications tend to have early admission to nursing homes and diminished survival.
  • Individuals with just tremors at the initial presentation tend to have a protracted benign course.
  • Individuals diagnosed with the disease at older age combined with hypokinesia/rigidity tend to have a much more rapid progression of the disease.

The disorder: leads to disability of most patients within ten years; has a mortality rate three times the normal population.

Parkinson’s cannot yet be cured (treatment can improve symptoms but the quality of life is often poor). A lot of financial and other resources are being expended on research to find a cure.

Differential Diagnosis

  • Essential tremor
  • Huntington chorea
  • Dementia with Lewy bodies
  • Progressive supranuclear palsy
  • Neuroacanthocytosis
  • Normal pressure hydrocephalus
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