Huntington’s disease is a rare genetic neurodegenerative disorder caused by an expansion of the HTT gene which codes for the protein huntingtin. Huntingtin is involved in neuronal function and brain development. People with the affected version of this gene begin to exhibit mild symptoms between the ages of 30 – 50. As the disease inevitably progresses, patients lose the ability to walk, talk, reason, and live independently.
What is Huntington’s Disease
According to the World Health Organization, five to seven people are affected for every 100,000 people. The basic symptoms of this condition vary but the most common affect cognition, movement, and personality or mood. While most cases begin during early middle age, the greater the expansion of the gene, the earlier the onset of the disease.
Childhood-onset Huntington’s, known as juvenile huntington’s disease (JHD) is caused by upwards of 60 repeats in the expanded section of the HTT gene, which usually has less than 25 repeats.
Most patients with HD will experience some form of the following:
- Cognitive Symptoms: tendency to get stuck on thoughts or actions, lack of control with outbursts, lack of awareness of one’s own behavior, difficulty in learning new information
- Movement Symptoms: involuntary jerking, muscle problems such as abnormal stiffness or contraction of muscles
- Psychiatric Symptoms: irritability, sadness, social withdrawal, fatigue, loss of energy, and frequent thoughts of suicide
Cause of Huntington’s Disease(HD)
The underlying cause of this disease is a codon repeat in the fourth chromosome. The sequence CAG, which stands for the bases cytosine, adenine, and guanine, is repeated between 14 and 28 times in the normal human version of this disease. Huntington’s disease is caused by a lengthening of this repeat sequence on reproduction, such that a child of someone with between 28 and 36 repeats of this section will inherit a gene with roughly 31-39 repeats of this section. In this particular example, the child would exhibit the disease while the parent would not, as the parent had less than 36 repeats. The next generation of offspring would have a greater number and so on.
While the nature of this mutation is not entirely understood, and the purpose of the huntingtin protein is only vaguely known, the characteristics of the disease are highly conserved between cases and individuals. Growing in our understanding of the role of huntingtin in brain function will shed light not only on new and better treatments but also on the inner workings of nervous tissue.
Diagnosis and characteristics of Huntington’s Disease(HD)
Diagnosis of Huntington’s disease is generally based on the results of a physical exam, a review of family medical history, and neurological and psychiatric examinations. If certain criteria are met, a genetic test will be done. If your parents are known carriers of the faulty gene, then a genetic test can confirm whether or not you will inherit the disease. Many are reluctant to find out, however, due to the life-altering effects of a diagnosis of this progressive, long-term, ultimately terminal, neurodegenerative disease.
To illustrate, the neurological examination is looking for:
- Motor Symptoms: such as reflexes, coordination, balance, and muscle strength
- Sensory Symptoms: such as sense of touch, hearing, vision and eye movement
- Psychiatric Symptoms: such as the patient’s mood and mental status
A physician may also order brain imaging tests such as a CT scan or an MRI to determine the structure and functionality of the patient’s brain versus a healthy brain of the same age. The physician will be looking for damage in areas or deformities that are not usual for a healthy brain. Then, to bring it all together the physician may order a genetic test to determine the quantity of repetitions a patient has for the disease.
The specific CAG repeat sequence codes for the amino acid glutamine. On degradation, increased quantities of glutamine produce increased quantities of the neurotransmitter glutamate, the primary excitatory neurotransmitter responsible for over 90% of neurotransmission. Excess quantities of glutamate cause known excitotoxicity, and nerve death due to excitotoxicity is consistent with the pathology of Huntington’s disease.
Current treatment options and best practices for HD
HD has no cure. Treatments are only palliative, and lifestyle modifications and therapy are usually helpful as the disease progresses into later stages. Some drugs can minimize the movement and mood symptoms of the disease, but may result in side effects that worsen other symptoms. Therefore, the treatment goals and plan are regularly reviewed and updated. Some examples of medications are the following:
- Tetrabenazine (Xenazine): used to calm the involuntary jerking and writhing movements (chorea) of HD. A serious side effect is the risk of worsening or causing depression in patients.
- Antidepressants (Zoloft): used to help a patient cope with their depression if it arises, but these medications can cause nausea, diarrhea, and low blood pressure.
What has proven successful to another extent is managing the disorder with family and caregivers. Loved ones create an environment that is organized and helps the patient deal with their behavioral & cognitive challenges, doing some of the following:
- Using calendars and schedules to help keep a regular routine
- Initiating tasks with reminders or assistance
- Prioritizing and organizing work or activities
- Breaking down tasks into manageable steps
- Creating an environment that is as calm, simple, and structured as possible
- Identifying and avoiding stressors that can trigger outbursts, irritability, depression, or other problems
- For school-age children or adolescents, consulting with school staff to develop an appropriate individual education plan
- Providing opportunities for the person to maintain social interactions and friendships as long as possible
Is endocannabinoid deficiency involved in HD?
The decrease in muscle contraction mediated by endocannabinoids makes the endocannabinoid system an attractive target for Huntington’s disease treatments because the disease causes overactive muscle contraction & movement. In addition, research has proven that the CB1 receptors, those involved in the motor effects of cannabis and produced in the brain naturally, are downregulated in parts of the brain as HD worsens; specifically so in an important region called the basal ganglia.
This region is responsible for motor control, as well as other roles such as motor learning, executive functions, behavior, and emotions. The action of the endocannabinoid system in this area of the brain is to regulate the ratio of production between excitatory neurotransmitters such as dopamine and glutamate, and inhibitory neurotransmitters, like serotonin and GABA.
By targeting the ECS in the specific cells which regulate glutamate production, excitotoxicity may be decreased and progression of the disease delayed.
Does CBD improve cases of Huntington’s disease?
In HD, neurons have an excess of glutamate precursor proteins, causing cells to intake too much calcium from being over excited. Excitotoxicity is caused because glutamate leads to an influx of calcium into the cell, causing the generation of an action potential. When too much glutamate stimulates the cell, it causes a toxic amount of calcium to flood the neuron, which compensates by initating apoptosis, or programmed cell death.
According to research conducted by Pazos MR and company, CBD oil enhances activation of CB1 & CB2 receptors, and activation of these receptors (by endocannabinoids, or THC and phytocannabinoids) leads to blockade of the calcium channels which pump calcium into the neuron following activation by glutamate. Cannabinoid receptors prevent the calcium influx which ultimately leads to cell death, and this effect has the following repercussions.
- Reduction in inflammation via activation of CB2 receptors
- Preserving or maintaining the balance of glutamate which means less toxicity, via activation of CB1 receptors
- Antioxidant effects mediated directly from CBD molecules which bind to the harmful free radicals released by calcium influx. These are the actual cause of calcium-mediated excitotoxicity, and by reducing the quantity of free radicals, CBD boosts its own effect on cannabinoid receptors.
CBD has none of the negative side effects of the medications currently used to delay death in patients with Huntington’s disease, and it has several highly effective mechanisms of action which alter the underlying pathology of the disease in addition to relieving acute symptoms. More research is needed to fully grasp the understanding of the CBD oil effects on Huntington’s disease, but it has already helped thousands to cope with this debilitating condition.