Therapieversuch mit einem ACTH-Fragment (ACTH 4–10) bei frühkindlichen Anfällen

Willig, R. P.; Lagenstein, I

doi:10.1007/978-3-662-38563-0_26

Cited by 14 publications

(5 citation statements)

References 4 publications

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“…The purpose of this study was to determine if the ACTH 4 -9 analogue (ORG 2766) would reduce the frequency of seizures without producing the side efTects of ACTH. tile spasms or Lennox-Gastaut syndrome; there was no improvement in their seizure frequency nor in their EEG (Willig and Lagenstein 1980). While the results of the current study are not dramatic, nevertheless, there was equivocal improvement in seizure frequency in several of the patients.…”

Section: Introductioncontrasting

confidence: 74%

“…All other anticonvulsants, as weIl as the ketogenic diet when in use, were maintained unchanged throughout thc study period. Quantitative records of seizures were maintained by the parents This was a prospective, double-blind, crossover evaluation of the ACTH4-9 analogue (ORG 2766) in four children with intraetable seizure disorders (Table 1) A study using the ACTH fragment (ACTH 4 _ 1O ) in seven children with hypsarrhythmia or Lennox-Gastaut syndrome did not show any improvement in seizure frequency nor improvement in the EEG (Willig and Lagenstein 1980). An analogue of ACTH 4 _ 9 (ORG 2766) has increased resistanee to proteolytic breakdown because of amino acid substitutions (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Trial of an ACTH_4-9Analogue (ORG 2766) in Children with Intractable Seizures

1982

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The ACTH4-9 Analogue (ORG 2766) is an orally administered neuropeptide which has been showed to have behavioral effects in human subjects, but does not have any steroidogenic effects, nor other significant side effects. This study was a double-blind, crossover trial of the ACTH4-9 analogue in four children with intractable seizures. There was some slight improvement in seizure frequency in two patients, with an equivocal improvement in a third child. A fourth child was unchanged, while the fifth dropped out of the study. There were no side effects from the therapy. This questionable improvement in seizure frequency in some of the most intractable patients with seizure disorders indicates the need to further assess this ACTH4-9 analogue in a larger study over a longer period of time.

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Section: Introductioncontrasting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Trial of an ACTH_4-9Analogue (ORG 2766) in Children with Intractable Seizures

1982

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“…Thus, we began an experiment with the adrenal inefTective ACTH-fragment (ACTH4-lo) in seleeted cases of infantile spasms ( Willig and Lagenstein 1980). 7 children (Table I) were treated with ACTH4-IO over a period of3-10 weeks with a dose of2 x 15 to 2 x 30 mg per die S.c. One patient received additionally 12 x 30 mg per die over 16 20 24 clock time Fig.2 Adrenal insufficiency due to long-term dexamethasone treatment in a child suffering from centrencephalic myoclonicastatic petit mal: when plasma cortisol was just normal (11 th day) there was already a positive effect in the EEG Similar morphologieal ehanges oeeurred during dexamethasone treatment and so a elear distinetion eould not be made between the effect of ACTH and glueoeortieoid.…”

Section: B) Investigations Of Adrenocortical Insufficiencymentioning

confidence: 99%

“…The application of other ACTH-analogues appears even more favourable (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) or 11-24) because it may be possible to find the amino acids sequence which leads to an anticonvulsive effect at the end ofthese molecules.…”

Section: B) Investigations Of Adrenocortical Insufficiencymentioning

confidence: 99%

Use of ACTH Fragments in Children with Infantile Spasms

Rp¹,

Lagenstein²

1982

Neuropediatrics

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Referring to the article of Pente/la et al in this issue of Neuropediatrics we report on experiences with ACTH therapy in infantile spasms. In addition we want to point out the reasons which led us to use ACTH fragments for therapeutic trials in children with infantile spasms.Adrenocorticotropic hormone (ACTH) has been a useful drug in the treatment of petit mal since 1950 (Klein and Livingstone 1950). The compound was successfully used in its natural form with 39 amino acids (ACTHI-39) and in its fragmented form with 24 amino acids (ACTHI-24), the latter being the most common and most frequently applied form of ACTH. We recently completed a prospective study on infan.. tile spasms and Lennox syndrome (Lagenstein et al 1978a, b) in which we administered an ACTH-fragment consisting of 23 amino acids (ACTHI-23). All the ACTH molecules mentioned caused marked hypercortisolaemia which was not sig.. nificantly different when induced by ACTHI-23 (Willig et al 1978). As a result maximal stimulated adrenals led to severe side efTects -these are familiar from Cushing's disease.Conventional ACTHI-24 was very efTective upon infantile spasms (Singer et al 1980). Particularly in infantile spasms beginning within the first year of life, and in centrencephalic myoclonic-astatic petit mal cases of older children ACTH seems to be a suitable drug and also seems to be most effective if it is applied within the first month of the spasm onset as far as infantile spasms are concemed.In spite of good seizure control with ACTH, physicians he.. sitate to administer corticotropins because the side effects may appear even more impressive than the seizures them.. selves when treatment is carried out for aperiod of 3 to 6 months at an ACTH dose of80 IV per day.After one of our patients on ACTH therapy had died from pneumonia, we strongly considered how the side effects could be reduced withoutjeopardizing the positive effects ofACTH. Our own observations during the hormonal seizure treatment led us to the conclusion that the therapeutical aministration ofACTH has a direct effect on the central nervous system and not via the adrenocortical hormones: a) Dose-dependency in relation to the effect of ACTH From the tenth treatment day on ACTH led to a maximal cortisol level of 100 J.1g/dl on average with large individual fluctuations. The moment of therapy success was not con.. nected to the level of cortisol. One patient who showed the highest cortisol plasma level (440 Jlg/dl) did not react to the ACTH therapy. This was an indication that ACTH has a direct effect upon the brain and possibly does not have an effect via the adrenal cortex. The fact that only 15 IU ACTH is required in order to achieve a maximal adrenocortical effect also supports this theory. In addition, the results which have been reported in the literature clearly indicate that therapy success is dependent on the ACTH dose level. In our opinion these facts indicate that ACTH acts directly on the brain. b) Investigations of adrenocortical insufficiencyWe had the opportunity of...

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“…6 children were examined by cranial C C T (Lagenstein et al 1979) before, 8 during and 6 after hormonal therapy (Table 11), thev were 5 girls and 3 boys from 5 months to 12 years. Except patient 8 they were treated with hormones for the first time.…”

Section: Patientsmentioning

confidence: 99%

Cranial Computed Tomography (CCT) Findings in Children Treated with ACTH and Dexamethasone: First Results

Lagenstein¹,

Rp²,

Kühne³

1979

Neuropediatrics

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8 children with different petit mal epilepsies were systematically treated with ACTH and dexamethasone. CCT examinations were performed before, during and after treatment. In all children severe cerebral changes. enlargement of ventricles and subarachnoid space developed during the initial phase of treatment with Depot-ACTH. Similar changes, but to a less severe degree, could be demonstrated during the phase of dexamethasone therapy thereafter. In all patients cerebral changes disappeared after hormonal treatment had ended. At this point many children had a developmental spurt, developmental relapses could not be observed. It is suggested that these reversible changes seen on CCT scans represent a form of morphological plasticity of brain structures. These results bear certain consequences as to the therapy of cerebral edema.

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Therapieversuch mit einem ACTH-Fragment (ACTH 4–10) bei frühkindlichen Anfällen

Cited by 14 publications

References 4 publications

Trial of an ACTH_4-9Analogue (ORG 2766) in Children with Intractable Seizures

Trial of an ACTH_4-9Analogue (ORG 2766) in Children with Intractable Seizures

Use of ACTH Fragments in Children with Infantile Spasms

Cranial Computed Tomography (CCT) Findings in Children Treated with ACTH and Dexamethasone: First Results

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Therapieversuch mit einem ACTH-Fragment (ACTH 4–10) bei frühkindlichen Anfällen

Cited by 14 publications

References 4 publications

Trial of an ACTH4-9Analogue (ORG 2766) in Children with Intractable Seizures

Trial of an ACTH4-9Analogue (ORG 2766) in Children with Intractable Seizures

Use of ACTH Fragments in Children with Infantile Spasms

Cranial Computed Tomography (CCT) Findings in Children Treated with ACTH and Dexamethasone: First Results

Contact Info

Product

Resources

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Trial of an ACTH_4-9Analogue (ORG 2766) in Children with Intractable Seizures

Trial of an ACTH_4-9Analogue (ORG 2766) in Children with Intractable Seizures