Fixing the Alzheimer’s Gene

The gene APOE has been heavily researched in connection with causing Alzheimer’s, with the latest research suggesting that the gene can be “fixed” through the administration of a lab-engineered APOE4 to the faulty gene, resulting in structural changes that make the APOE4 gene behave more like the APOE3 gene, the inoffensive gene.

Applying the modified APOE4 gene to human neurons corrected the defects, restoring normal cell function, prolonging cell life and erasing the signs of the disease.

If someone has one copy of the APOE4 gene, their risk of developing Alzheimer’s increases three fold and if they have two copies their risk is increased twelve fold. The role of APOE in the body is to provide instructions for synthesising proteins and in combination with fats, liproprotein complexes are formed which are used to transport cholesterol through the blood stream.

The E4 variant has been strongly linked to the build up of beta-amyloid plaques in the brain- however this was only observed after the gene was studied in human cells in the lab- in mice, there was no beta-amyloid build up in the neurons. This is often a large stumbling block in developing effective Alzheimer’s treatments- new drugs model perfectly in mice, however in humans there are discrepancies in terms of their efficacy. This new research represents a new frontier in developing effective treatments.

1. [Accessed 21/05/2018]

Halting Alzheimer’s Disease with SERCA activator

Research published by Purdue University indicates the possibility of slowing down or even halting Alzheimer’s. The research presents the SERCA activator as reducing cellular stress and preventing cell loss through the correction of calcium ions within the cell- this signifies a new frontier in therapeutic strategies for targeting neurodegenrative drug development.

Typically, brain cell loss occurs due to an imbalance in calcium ions, the research conducted aims to directly rectify this imbalance. The researchers developed molecules that target calcium handling proteins- in this case SERCA. Researcher’s focused on the role of the SERCA activator in neurodegenrative disorders. The aim of this study was primarily geared towards developing a drug that protects against cellular injury.

The evidence for the positive on Alzheimer’s is promising, the SERCA activator allowed for a 60% reduction in beta-amyloid plaques. The SERCA activator can also reverse apoptosis of cells, essentially reviving them from death. This is significant as the prevention of apoptosis can directly prevent neurodegeneration. This development is not only significant for treating Alzheimer’s but also other neurodegenrative diseases such as Parkinson’s and ALS.


Image taken from original study (2) demonstrating how the SERCA Activator may work. 

1. – Original Article

2. – Original Study

Charles Bonnet Syndrome

After watching Oliver Sacks’ TED talk, “What Hallucination Reveals About Our Minds”, I was intrigued by a dementia patient who was experiencing hallucinations after going blind through macular degeneration. Sacks had concluded that she was suffering from Charles Bonnet Syndrome, or also called Visual Release Hallucinations. This post aims to give an outline of the syndrome, and explore treatments and causes.

Charles Bonnet Syndrome (CBS) is characterised as a type of psychophysical visual disturbance and sufferers are blind or severely visually impaired and experience intricate visual hallucinations. A characteristic of these hallucinations is the that they appear “lilliputian”, i.e. they are smaller than usual. Cartoons are typical hallucinations, as Sacks’ patient commonly experienced. The significant part of CBS is that the sufferer’s are aware that the hallucinations are not real.

The prevalence of CBS was explored in an Australian Study which found that amongst adults over 65, 17.5% experienced these hallucinations. However the incidence may be higher as sufferer’s may be fearful of reporting the hallucinations for fear of being labelled mentally ill.

The syndrome can be developed after damage to the bilateral optic nerve occurs through methyl alcohol poisoning. Macular degeneration combined with restriction of the visual field after glaucoma can also predispose CBS. Diabetes-related eye conditions and cataracts can also lead to visual hallucinations. The hallucinations experienced in CBS can be heightened through intense emotional distress such as grief, or depression, sensory deprivation, strokes and impaired cognitive abilities.

The hallucinations occur as a result of the brain reacting to losing sight, the brain reacts to visual loss by producing images that had previously been seen, as it is no longer receiving any visual input.

There are not express treatments for CBS, however it has been observed that after the patients are aware that the hallucinations are not part of a mental disorder, but a reaction to loss of sight, the hallucinations become less frequent. It is believed that no treatment is required due to the fact that the hallucinations are believed not to be permanent and will eventually fade away on their own.

However, it has been found that drugs used to treat Parkinson’s, dementia and epilepsy have been found to alleviate the hallucinations- but it must be known that these medications have side-effects, and it is also possible that these medications intensify the hallucinations.


Exploration in the aetiology of Autism Spectrum Disorder

A common question associated with Autism Spectrum Disorder (ASD), is what causes it? The precise cause is unknown, although there is significant research into the aetiology of the disorder that provides some insight.

ASD is believed to be caused by multiple influences such as environmental, biological and genetic factors. The influences of these factors may explain the spectrum of behaviour observed in people with ASD. ASD may be associated with various conditions affecting brain development such as maternal rubella (including other viral diseases of the central nervous system) or post-encephalitic neuroinflammation but this link remains unclear. Some research has hinted at the possibility of ASD being caused by fragile X syndrome, encephalitis and untreated phenylketonuria.

Fragile X syndrome is a genetic condition which causes developmental problems, including ASD. It affects males more severely than females, and affected persons characteristically have delayed speech and language development. One third of females affected are intellectually disabled with most males having moderate intellectual disability. About one-third of people with fragile X syndrome have features of ASD. Fragile X syndrome is the most prevalent known single gene cause of ASD.

Autoimmune encephalitis is where the immune system attacks the brain- impairing its function. Research has suggested that children with ASD have a brain pathology indicating ongoing neuroinflammation or encephalitis. It is estimated that around 69% of children with ASD have neuroinflammation- however children who are diagnosed with ASD are not typically tested for encephalitis. This means that if a child has developed ASD as a result of encephalitis, they could receive treatment that reduces the deficits of ASD.

Phenylketonuria is a fault in the metabolism that leads to the decrease in metabolic activity involving the amino acid phenylalanine. It is an inherited disorder and is due to the mutation in the PAH gene which subsequently influences the levels of the enzyme phenylalaline hydroxylase- significantly lowering them. Left untreated, it can lead to intellectual disability and possibly autism.

Maternal rubella is associated with ASD, it was found that children with ASD had an “altered immune response to rubella vaccination” (5), this suggested that they had already been affected by rubella. With Chess (1971) finding that children with congenital rubella had an increased incidence of ASD. It was suggested from this that congenital rubella of the central nervous system could produce the complex and severe social deficits of ASD.

This is only small insight into the possible aetiology of autism spectrum disorder, however current research is providing more evidence for the possible causes of ASD.

1. [Accessed 03/05/2018]
2. [Accessed 03/05/2018]
3. Kern, Janet K., et al. “Relevance of Neuroinflammation and Encephalitis in Autism.” Frontiers in Cellular Neuroscience, vol. 9, 2016, doi:10.3389/fncel.2015.00519.

Correlation between loss of sleep and Alzheimer

Current research suggests that there is a link between the lack of sleep and the subsequent development of Alzheimer. Multiple articles and studies have been published exploring this subject and I have provided some links to them below.

A study conducted in April 2018 by the National Institute of Alcohol Abuse and Alcoholism found that losing only one night of sleep leads to an increase in beta-amyloid, a protein associated with Alzheimer’s disease found in the brain. The beta-amyloid proteins coagulate forming amyloid plaques in the brain- these plaques are typical traits of Alzheimer. Beta-amyloid is a “metabolic waste product present in the fluid between brain cells”.
The formation of beta-amyloid plaques is believed to directly impair neurone communication and the plaques are considered neurotoxic.

A further study that also explores the link between sleep deprivation and Alzheimer was conducted by the Centre for Translational Neuromedicine. This study discovered that the glymphatic clearance pathway, which clears waste for the central nervous system, is ten time more active whilst we are asleep compared to when we are awake. The glymphatic system clears away beta-amyloid plaques and without sufficient sleep the system is unable to clean.

It was also found in a study at the University of Rochester Medical School that whilst mice slept, cells in the brain shrank, facilitating a greater volume of fluid to pass between the cells, aiding the removal of the buildup of neurotoxic molecules.

Furthermore, scientists at the University of Toronto found that adequate sleep led to the inhibition of the APOE-E4 gene- a gene typically associated with the development of late-onset Alzheimer. The study also showed that participants who carried the APOE-E4 gene and slept well had better retention of memories and thinking skills.

The results produced by these studies provides convincing evidence for the link between sleep deprivation and the development of Alzheimer- however further studies are needed for this relationship to be understood completely.

1. NIH/National Institute on Alcohol Abuse and Alcoholism. “Lack of sleep may be linked to risk factor for Alzheimer’s disease: Preliminary study shows increased levels of beta-amyloid.” ScienceDaily. ScienceDaily, 13 April 2018. .
2. [Accessed 30/04/2018]
3. [Accessed 30/04/2018]

Reversal of Autism’s Social Deficits through use of Anti-Cancer Drug

An article published on Science Daily (linked below) led me to write this post about the possibility of the alleviation of the social deficits associated with Autism Spectrum Disorder, it detailed the possibility of using an anti-cancer drug to treat the symptoms of ASD.

Current treatments of Autism Spectrum Disorder include behaviour management techniques, the administration of psychotropic drugs including selective serotonin re-uptake inhibitors (SSRIs) and anti-psychotics. Behaviour management techniques include teaching positive behaviours and reducing negative ones, this can include teaching interpersonal skills and reducing anti-social behaviours such as echolalia and inconsistent eye contact. The prescription of SSRIs is meant to treat conditions such as depression, anxiety and obsessive compulsive behaviours that are closely associated with the Disorder.  Anti-psychotics are commonly used in treating the symptoms; these include treating aggression, self injury and hyperactivity.

New research conducted at the University of Buffalo suggests that the use of a single drug instead of a combination of treatments, may be efficacious in mitigating the anti-social behaviours associated with the Disorder. The research presented the possibility that the administration of low doses of romidepsin, a drug typically used to treat cutaneous and peripheral T-Cell Lymphoma, could be effective in reversing social deficits. During the research, mice lacking in the gene Shank-3, a risk factor in Autism Spectrum Disorder, were administered very low doses of romidepsin in a three-day treatment. The effects of the administration were long lasting, spanning three weeks. What should be noted is that there is currently no treatment available to treat the main symptom of ASD- the social deficits.

Shank-3 typically provides instructions for synthesising proteins that are found most commonly in the brain. The gene plays a role in the function of the synapses supporting the connections between neurons. Gene mutations within the Shank-3 gene have been identified in people with ASD. The mutations either completely inhibit the production of the gene, or disturbs the production of the proteins. It is currently not known how this mutation relates to the development of ASD however it is hypothesised that the disturbance of the connection between neurons is an influencing factor.

Romidepsin works by reconstituting the expression of genes and their functions through the use of epigenetic mechanisms. This is done by genes being changed through influences not including DNA sequencing.

This research indicates a revolutionary new field of treatment for people living with the ASD, and could lead to exciting new developments in treatment and management of the Disorder.

Original Article: [Accessed 30/04/2018]

1. [Accessed 30/04/2018]
2. [Accessed 30/04/2018]
3. [Accessed 30/04/2018]