Today’s post
was triggered by an intriguing comment left on this blog.
As we have
seen in previous posts, the single gene causes of “autism” like fragile X and
Rett syndrome are themselves on a spectrum, with some people worse affected than
others. Boys almost always being more
severely affected than girls.
It also
appears possible that a partial dysfunction of this same gene/protein may lead
to a much milder version of these same syndromes.
Rett
syndrome is well studied and as we saw in the earlier post about growth factors
in autism, one key feature is an almost complete lack of Nerve Growth Factor
(NGF). Reduced levels of NGF are
associated with several diseases and also the aging process. In many cases of Mild Cognitive Impairment
(MCI), as seen in dementia in older people, reduced NGF can be the root
problem.
Rett Syndrome
Rett syndrome usually gets grouped as part of autism.
Almost all people with Rett syndrome are female; here is
why.
Rett syndrome is caused by mutations in the gene MECP2 located on the X chromosome. Because the disease-causing gene is located on the X chromosome, a female born with an MECP2 mutation on her X chromosome has another X chromosome with an ostensibly normal copy of the same gene, while a male with the mutation on his X chromosome has no other X chromosome, only a Y chromosome; thus, he has no normal gene. Without a normal gene to provide normal proteins, the male fetus is unable to slow the development of the disease, hence the failure of male fetuses with a MECP2 mutation to survive.
Rett syndrome is caused by mutations in the gene MECP2 located on the X chromosome. Because the disease-causing gene is located on the X chromosome, a female born with an MECP2 mutation on her X chromosome has another X chromosome with an ostensibly normal copy of the same gene, while a male with the mutation on his X chromosome has no other X chromosome, only a Y chromosome; thus, he has no normal gene. Without a normal gene to provide normal proteins, the male fetus is unable to slow the development of the disease, hence the failure of male fetuses with a MECP2 mutation to survive.
MECP2 is
known to play a wider role in some
autism, epilepsy and MR/ID
We saw that the Italian Nobel Laureate, Rita Levi-Montalcini, who discovered Nerve Growth factor (NGF), maintained her mental sharpness into her 90s by taking her homemade NGF eye drops in her old age.
Human Growth Factors, Autism and the Centenarian Nobel Laureate
The problem
with NGF is that it does not cross the blood brain barrier (BBB), so there are
no NGF tablets. Rita’s solution was eye
drops; I expect the nasal route might also be possible.
Dompe Farmaceutici are developing
NGF eye drops as an orphan drug to treat Retinitis pigmentosa
Bypassing
the BBB is of great interest to medical science as we have seen in earlier
posts.
Stimulating NGF with Hericium Erinaceus (Lion’s Mane
Mushroom)
There is a
surprising amount of literature about the use of a mushroom called Hericium
Erinaceus, or Lion’s Mane, to treat various neurological conditions. The made mode of action is stimulating production
of NGF.
It was Lion’s
Mane that the reader of this blog is giving to his daughter. This is not typical autism, but in this era of
diagnosing almost any childhood developmental dysfunction as autism, I expect
autism is label many would apply to it.
“Our
14 year old daughters previous diagnoses of PDD has recently been dropped,
re-evaluated, and named Mild Cognitive Disability with Anxiety and Dementia.
This turned out to be a great turn of phrase for us because we began to see and
approach her condition differently. To begin with we started look at the
similarities between her poor working memory and irritability as more similar
to the dementia you would see in early stages of Alzheimer’s than something
that could be treated with ABA as we had previously tried”
Is this a mild version of Rett
Syndrome, like the Zappella variant is?
Anyway, it responds to a therapy that
increases NGF, a key deficit in Rett Syndrome.
Studies supporting the use of Hericium Erinaceus / Lion’s Mane/
Yamabushitake and also Amyloban 3399
Lion’s mane
is also called Yamabushitake and a rather expensive
concentrated product derived from it is called Amyloban 3399.
As always, the problem with supplements is quality control, lack of standardization and even contamination.
There would seem to be the potential to make an effective drug based on Lion’s Mane.
It would also seem logical to trial Dompe Farmaceutici’s NGF eye drops in children with
Rett Syndrome and in older people with early dementia, not to mention adults
with schizophrenia (see study on Amyloban 3399
below).
Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial.
Abstract
A double-blind,
parallel-group, placebo-controlled trial was performed on 50- to 80-year-old
Japanese men and women diagnosed with mild cognitive impairment in order to
examine the efficacy of oral administration of Yamabushitake (Hericium
erinaceus), an edible mushroom, for improving cognitive impairment, using a
cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R).
After 2 weeks of preliminary examination, 30 subjects were randomized into two
15-person groups, one of which was given Yamabushitake and the other given a
placebo. The subjects of the Yamabushitake group took four 250 mg tablets
containing 96% of Yamabushitake dry powder three times a day for 16 weeks.
After termination of the intake, the subjects were observed for the next 4
weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed
significantly increased scores on the cognitive function scale compared with
the placebo group. The Yamabushitake group's scores increased with the duration
of intake, but at week 4 after the termination of the 16 weeks intake, the
scores decreased significantly. Laboratory tests showed no adverse effect of
Yamabushitake. The results obtained in this study suggest that Yamabushitake is
effective in improving mild cognitive impairment.
Our group
has been conducting a search for compounds for dementia derived from medicinal
mushrooms since 1991. A series of benzyl alcohol derivatives (named hericenones
C to H), as well as a series of diterpenoid derivatives (named erinacines A to
I) were isolated from the mushroom Hericium erinaceum. These compounds
significantly induced the synthesis of nerve growth factor (NGF) in vitro and
in vivo. In a recent study, dilinoleoyl-phosphatidylethanolamine (DLPE) was
isolated from the mushroom and was found to protect against neuronal cell death
caused by b-amyloid peptide (Ab) toxicity, endoplasmic reticulum (ER) stress
and oxidative stress. Furthermore, the results of preliminary clinical trials showed that the mushroom
was effective in patients with dementia in improving the Functional
Independence Measure (FIM) score or retarding disease progression.
Reduction of depression andanxiety by 4 weeks Hericium erinaceus intake.
Abstract
Hericium erinaceus, a well
known edible mushroom, has numerous biological activities. Especially
hericenones and erinacines isolated from its fruiting body stimulate nerve
growth factor (NGF) synthesis, which expects H. erinaceus to have some effects
on brain functions and autonomic nervous system. Herein, we investigated the
clinical effects of H. erinaceus on menopause, depression, sleep quality and
indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center
for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep
Quality Index (PSQI), and the Indefinite Complaints Index (ICI). Thirty females
were randomly assigned to either the H. erinaceus (HE) group or the placebo
group and took HE cookies or placebo cookies for 4 weeks. Each of the CES-D and
the ICI score after the HE intake was significantly lower than that before. In
two terms of the ICI, "insentive" and "palpitatio", each of
the mean score of the HE group was significantly lower than the placebo group.
"Concentration", "irritating" and "anxious"
tended to be lower than the placebo group. Our results show that HE intake has the possibility to
reduce depression and anxiety and these results suggest a different mechanism
from NGF-enhancing action of H. erinaceus.
Peripheral Nerve Regeneration Following Crush Injury to RatPeroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.:Fr) Pers. (Aphyllophoromycetidea
We treated 10 patients with schizophrenia in this study,
randomly selected by each doctor, working at six different institutions.
Patients ranged across age, duration of illness, sex, or psychotropic
drugs used.
All patients were refractory to currently available antipsychotic agents, but improved without exception and with no adverse
reactions.
Average scores on the positive and negative syndrome scale (PANSS) improved significantly for all items, including positive, negative, and general
psychopathology.
Case Report:
Recovery from Schizophrenia Using AmylobanⓇ3399, Compounds Extracted from Hericium erinaceum
AmylobanⓇ3399---contains Amycenon, a
standardized extract of HE containing hericenones and amyloban – and is
currently being tested for safety as a health food supplement (Mori, Inatomi,
Ouchi et al., 2009). A clinical trial with 8 volunteers was conducted to demonstrate
the cognition-enhancing properties of AmylobanⓇ3399 (Lotter,
2012). Results of the study showed that AmylobanⓇ3399 improved
mood, memory and sense of wellbeing. Overall AmylobanⓇ3399 was
generally well tolerated.
Schizophrenia is the most devastating disease of the major psychoses.
It has been repeatedly observed in clinical practice that although positive
symptoms may be reduced within a few week treatment period, while it takes
months or years to see improvements in cognitive symptoms. Atypical neuroleptic
clozapine is associated with reduced liability for extrapyramidal symptoms and
is effective in treatment-resistant schizophrenia. However, adverse effects
limit the widespread use of clozapine.
Amyloban3399 was originally thought to
be a drug for dementia.
However, based on my clinical observation, I asked a
schizophrenia patient presented in this report to take AmylobanⓇ3399. He had
been treatment-resistant and suffered from severe side effects for more than 30
years. He agreed to take Amyloban3399 and he has
experienced dramatic life improvements and has been doing quite well for these three
years.
Conclusion
Most autism variants appear to have high NGF, so the therapies
discussed here relate to Rett Syndrome and other low NGF variants of autism, not to mention dementia.
Signs of Rett syndrome that are not similar to autism:
- affects almost exclusively girls
Signs of Rett syndrome
that are similar to autism:
·
incontinence
·
screaming fits
·
inconsolable crying
·
breath holding, hyperventilation & air swallowing
·
avoidance of eye contact
·
lack of social/emotional reciprocity
·
markedly impaired use of nonverbal behaviors to regulate
social interaction
·
loss of speech
·
sensory problems
Signs of Rett syndrome that are also present in cerebral palsy (regression of the type seen in Rett
syndrome would be unusual in cerebral palsy; this confusion could rarely be
made):
·
possible short stature, sometimes with unusual body
proportions because of difficulty walking or malnutrition caused by difficulty
swallowing
·
delayed or absent ability to walk
·
gait/movement difficulties
·
ataxia
·
microcephaly in
some - abnormally small head, poor head growth
·
gastrointestinal problems
·
some forms of spasticity
·
chorea -
spasmodic movements of hand or facial muscles
·
dystonia
·
bruxism –
grinding of teeth
In people with low NGF, therapies known to increase it, look well worth
investigating.