Nucleotides in the Management of Neuropathies

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Dr. Ravi Paul
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OUTLINE

• How do we treat peripheral neuropathies?

• Who are our real competitors?

• Take home messages

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HOW DO WE TREAT PERIPHERAL NEUROPATHIES??
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Peripheral neuropathies
General information
Peripheral neuropathies are caused by damage or
injury to the nerves of the peripheral nervous
system that transfer information to and from the
brain and spinal cord from and to the skin,
muscles and other parts of the body.  Neuropathic
pain is one of the symptoms can negatively
impact a patients quality of life. 
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Peripheral neuropathies
General information

• Neuropathic pain guidelines include

https//www.pharmaceutical-journal.com/research/re
view-article/treatments-for-neuropathic-pain/20203
641.article?firstPassfalse
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Global burden of peripheral neuropathies
Background
High Prevalence of neuropathic pain
Market Share of Neuropathic Pain by Indication,
2016
NP-Neuropathic Pain PDN- Painful Diabetic
Neuropathy PHN Postherpetic Neuralgia
Source Decision Resources Group, March 2019
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Pharmacological treatment of Neuropathic pain

• Three drug classes have received strong
  recommendations for first-line therapy in all
  guidelines
• tricyclic antidepressants, particularly
  amitriptyline
• serotonin-norepinephrine reuptake inhibitors
  (SNRIs) such as duloxetine
• the calcium channel alpha-2-delta ligands
  gabapentin and pregabalin.

Source Decision Resources Group, March 2019
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Pharmacological treatment of Neuropathic pain

• A review of Neuropathic Pain From Guidelines to
  Clinical Practice. Giorgio Cruccu and Andrea
  Truini. Pain Ther. 2017 Dec 6 (Suppl 1) 3542.
  Published online 2017 Nov 24. doi 10.1007/s40122-
  017-0087-0

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Pharmacological treatment of Neuropathic pain
Source Decision Resources Group, March 2019
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There is an inadequate response to drug
treatments in patients with neuropathic pain.
Constitutes a substantial unmet need for these
patients
Finnerup et al. Lancet Neurol 201514162-73.
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Peripheral neuropathies

• Limitations to guidelines treatments

Side effects
Incomplete pain relief
https//www.pharmaceutical-journal.com/research/re
view-article/treatments-for-neuropathic-pain/20203
641.article?firstPassfalse
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PERIPHERAL NEUROPATHY
Painkiller

• Tricyclic antidepressants, amitriptyline
• Serotonin-norepinephrine reuptake inhibitors
  (SNRIs) such as duloxetine
• Calcium channel alpha-2-delta ligands gabapentin
  pregabalin

Nerve damage
Symptomatic Rx Pain
Inflammation/abnormal excitability
Degenerative affection of a nerve or nerves (loss
of part of the myelin sheath)
Sensitive and motor disorders according to
localization as tingling or burning, and loss of
sensation.
Nucleotides
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RESTORING CONNECTIONS
Acting at the root of the problem
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Acting at the root of the problem
Nucleotides promote peripheral nerve regeneration
specially for those patients with peripheral
neuropathies improving their quality of life
Increasing myelin sheath regeneration
Increasing motor neuron conduction
Relieving Symptoms pain,
hypersensitivity, paraesthesia
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Nucleo indications

• Dymielinating and neuropathic conditions in which
  nerve regeneration plays a role

Osteoarticular neuropathy Herniated disc,
sciatica, lumbalgia, carpal tunnel syndrome
Metabolic neuropathy Diabetes, Alcoholic
polineuritis
PERIPHERAL NERVE DAMAGE
Toxic substances Post-chemo, alcoholism..
Infectious neuropathy Herpes Zoster, HIV
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Who can prescribe Nucleo?

• Neuropathic back pain
• Diabetic Neuropathy

• GPs
• Traumatology
• Neurology
• Endocrinology
• Rheumatology
• Internal Medicine
• Pain Units

• First option Neuropathic Back pain Diabetic
  neuropathy
• Second option the rest of the neuropathies

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WHO ARE OUR REAL COMPETITORS?
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Nucleo CMP vs
TREATMENT GUIDELINES??
VIT B COMPLEX PRODUCTS??
ALFA LIPOIC ACID PRODUCTS?? (Thioctic acid)
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Who are our competitors?
TREATMENT GUIDELINES
https//www.pharmaceutical-journal.com/research/re
view-article/treatments-for-neuropathic-pain/20203
641.article?firstPassfalse
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Peripheral neuropathies

• Limitations to guidelines treatments

Side effects
Incomplete pain relief
https//www.pharmaceutical-journal.com/research/re
view-article/treatments-for-neuropathic-pain/20203
641.article?firstPassfalse
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PERIPHERAL NEUROPATHY
GUIDELINES TREATMENTS

• Tricyclic antidepressants, amitriptyline
• Serotonin-norepinephrine reuptake inhibitors
  (SNRIs) such as duloxetine
• Calcium channel alpha-2-delta ligands gabapentin
  pregabalin

Nerve damage
Symptomatology Pain
Inflammation/abnormal excitability
Degenerative affection of a nerve or nerves (loss
of part of the myelin sheath)
Sensitive and motor disorders according to
localization as tingling or burning, and loss of
sensation.
Nucleotides
CO-TREATMENTS

• Painkillers treat the pain
• Nucleotides act on the nerve regeneration

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Who should we fight against?
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Alpha-lipoic acid

• Alpha lipoic acid (ALA) is a fatty acid that acts
  as a strong antioxidant 
• It can manage a tissue-damaging process called
  oxidative stress. Oxidative stress is a part of
  the diabetic neuropathy disease process. 
• It also has been shown to reduce blood sugar
  levels (only in patients with type 2 diabetes)
• Doses 600-1800mg per day
• Safety analysis showed a dose-dependent increase
  in nausea, vomiting, and vertigo

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Alpha-lipoic acid
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Alpha-lipoic acid vs Nucleo
Clinical evidence with positive results only in
Diabetic neuropathies!!
Effective in the Treatment of neuropathies of
osteoarticular (sciatica, radiculitis, etc.),
metabolic (diabetic, alcoholic polyneuritis,
etc.), infectious (herpes zoster) origin, and a
frigore. Neuralgia of the Facial, Trigeminal,
Intercostal, Lumbago
Not effective in neuropathies caused by
compressive disorders or oncologic treatment
Lower doses than 600mg dont seem to
work!! High-dose ALA is not completely tolerated
by the elderly
Doses of 1 or 2 capsules twice a day Well
tolerated and safe In Children as well
There are alterations in rates of metabolism of
different formulations of lipoic acid
manufactured by different suppliers
reliability??
Formulated under GMP and quality controls of a
pharmaceutical company
Interactions with diabetes pharmacological
treatments
No interactions nor reported side effects
Its a food supplement!!
Its a drug!!
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Pregabalin
Gradual increase of the dose of pregabalin not
possible
Posology of Pregabalin for Neuropathic Pain
Associated with Diabetic Peripheral Neuropathy in
Adults The maximum recommended dose of Pregabalin
is 100 mg three times a day (300 mg/day 4
capsules) in patients with creatinine clearance
of at least 60 mL/min. Begin dosing at 50 mg
three times a day (150 mg/day). The dose may be
increased to 300 mg/day within 1 week based on
efficacy and tolerability. Although LYRICA was
also studied at 600 mg/day, there is no evidence
that this dose confers additional significant
benefit and this dose was less well tolerated. In
view of the dose-dependent adverse reactions,
treatment with doses above 300 mg/day is not
recommended

• High prevalence of side effects
• Feeling lightheaded, dizzy, sleepy, having
  blurred eyesight, or a change in thinking
  clearly.
• Change in balance.
• Weight gain.
• Muscle pain.
• Headache.
• Shakiness.
• Dry mouth.
• Emotional ups and downs.
• Nausea, upset stomach or throwing up. 

Lower doses than 600mg dont seem to
work!! High-dose ALA is not completely tolerated
by the elderly
Indicated in adults and children over 12 years old
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Vitamin B complex

• Vitamin B1 makes a further contribution to normal
  heart function and plays such as vitamins B6 and
  B12 play a role in the normal function of the
  nervous system.
• Vitamins B6 and B12 contribute to normal
  formation of red blood cells, which provide for
  the transport of oxygen in the blood. In
  addition, they contribute to the normal function
  of the immune system.
• Dosage 1 Tablet per day
• Products with a high concentration of vitamins
• Contraindicated if you have Kidney or liver
  disease
• Interactions with many medicines.
• Treatment should not exceed 15 days

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Vitamin B vs Nucleo
Prevention and treatment of a deficiency of
vitamins B1, B6 and B12
Effective in the treatment of neuropathies of
osteoarticular (sciatica, radiculitis, etc.),
metabolic (diabetic, alcoholic polyneuritis,
etc.), infectious (herpes zoster) origin, and a
frigore. Neuralgia of the Facial, Trigeminal,
Intercostal, Lumbago
Indicated in adults and children over 14 years old
Not to be taken in kidney or liver disease
Interacts with many medications Levodopa
(medicine to treat Parkinson's disease),
Phenobarbital, phenytoin (used to treat
epilepsy)., Altretamine (to treat cancer),
Amiodarone (heart), Neuromuscular blocking drugs,
5-fluorouracil (in some types of cancer)
Doses of 1 or 2 capsules twice a day Well
tolerated and safe Children also
Nucleotides favour myelin sheath regeneration and
axonal function recovery
Treatments no longer than 15 days Vitamin B6
for a long period causes peripheral neuropathies
Clinical studies with long term treatments (over
6 months)
Vitamin B6 can cause photosensitivity
No interactions reported
Other side effects Nausea, vomiting, headache,
drowsiness, paresthesia (tingling in the arms and
legs), and rash (redness or swelling)
No side effects reported
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NUCLEOTIDES
VITAMIN B COMPLEX
ALPHA-LIPOIC ACID
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• Growing prevalence of Neuropathic pain with
  difficult therapeutic results
• Nucleotides offer an effective solution for nerve
  regeneration
• The only product with UMP with proven efficacy in
  the treatment of nerve regeneration.
• For use in patients with both acute or chronic
  peripheral neuropathies
• Safe and unique therapy with causal mode of
  action.
• Containing uridine and cytidine which are normal
  constituents of our metabolism
• No contraindications or side effects and no
  interactions with others drugs have been
  described.
• It can also be administered to children

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TAKE HOME MESSAGE
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Key points on the peripheral neuropathies and
nucleotides

• Neuropathy has two components etiology and
  symptomatology.

• Peripheral neurons can regenerate after injury
• Peripheral neurons do not synthesize the
  nucleotides they need
• Nucleotide exogenous intake is conditionally
  essential
• Nucleotides are the only treatment that restores
  the neuronal function regenerating the myelin
  sheath
• They act directly upon the injury and indirectly
  on the symptoms

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Key points on Nucleo CMP Forte

• Only drug for the treatment of peripheral
  neuropathy with a mechanism of action that
  repairs the myelin sheath.
• Specific indication for neuropathic pain.
• Very good safety profile compared to placebo.
• Can be combined with standard treatment for
  neuropathic pain.
• New publications about benefits of nucleotides on
  peripheral neuropathies

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ARE THERE ANY QUESTIONS?
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THANK YOU VERY MUCH FOR YOUR ATTENTION
Dr. Ravi Paul
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FAQS
What are the common side effects reported by the
patients? Drowsiness, dizziness, constipation,
stomach upset, blurred vision, or dry
mouth/nose/throat may occur.
How long can one take? 6 weeks with twice a day
dose
Effect of the Nucleus CMP forte in 46 patients
with progressive spastic paraparesis. Randomized
and blind study. The medication caused a modest
improvement in patients with progressive spastic
paraparesis and was free of side effects.
How long does Nucleo CMP take to work? Patients
usually have a statistically positive effect on
the symptoms after 10 days of treatment according
to Neurological Symptom Score.